LEMBAR PENGESAHAN

Nama Fakultas Tingkat

: Eva Apiani : Kedokteran Umum : Universitas Trisakti Jakarta : 3 September 2012 9 November 2012

Bidang Pendidikan : Ilmu Kandungan dan Kebidanan Periode Kepaniteraan Klinik Judul

: Sebuah Penelitian untuk Bandingkan Efektivitas Misoprostol, Oksitosin, Methyl-ergometrine dan Ergometrin-Oksitosin dalam Mengurangi kehilangan Darah di dalam Manajemen persalinan kala 3

Diajukan Pembimbing

: 24 Oktober 2012 : Letkol Kes dr. Zakaria, Sp. OG

Telah Diperiksa dan Disahkan Tanggal Mengetahui :

Ketua SMF Ilmu Kandungan dan Kebidanan RSPAU dr. Esnawan Antariksa Jakarta

Pembimbing

Letkol Kes dr. Zakaria, Sp. OG

Letkol Kes dr. Zakaria, Sp. OG

DAFTAR ISI Lembar pengesahan .1 Daftar isi ....2 Journal : A Study to Compare the Efficacy of Misoprostol, Oxytocin, Methyl-ergometrine and ErgometrineOxytocin in Reducing Blood Loss in Active Management of 3rd Stage of Labor Abstract Objective ....4 Study Design...4 Results.............4 Conclusion..5

Introduction Aims and Objectives..6 Material and Method....6 Results.....7 Conclusion....12 References.....13

JURNAL : Sebuah Penelitian untuk Bandingkan Efektivitas Misoprostol, Oksitosin, Methyl-ergometrine dan Ergometrin-Oksitosin dalam Mengurangi kehilangan Darah di dalam Manajemen persalinan kala 3
Abstrak

Objektif ....15 Design penelitian.....15 Hasil .........15 Kesimpulan ..16

Pengantar 16 Maksud dan Tujuan ...16 Bahan dan Metode......17 Hasil .....18 Kesimpulan ......22 Daftar pustaka......24

J Obstet Gynaecol India. 2011 August; 61(4): 408412. Published online 2011 September 23. doi: 10.1007/s13224-011-0060-5 PMCID: PMC3295875

A Study to Compare the Efficacy of Misoprostol, Oxytocin, Methylergometrine and ErgometrineOxytocin in Reducing Blood Loss in Active Management of 3rd Stage of Labor
J. T. Gohil
1,2

and Beenu Tripathi1

Author information Article notes Copyright and License information Go to: Abstract Objectives The purpose of the study was to compare the efficacy of misoprostol 400 g per rectally, injection oxytocin 10 IU intramuscular, injection methylergometrine 0.2 mg intravenously and injection (0.5 mg ergometrine + 5 IU oxytocin) intramuscular on reducing blood loss in third stage of labor, duration of third stage of labor, effect on haemoglobin of the patient, need of additional oxytocics or blood transfusion and associated side effects and complications. Study Design A prospective non-randomized uncontrolled study was carried out in the Department of Obstetrics and Gynecology, SSG Hospital and Medical College, Baroda enrolling 200 women and dividing them into four groups. Active management of 3rd stage of labor was done using one of the 4 uterotonics as per the group of the patient. The main outcome measures were the amount of blood loss, the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 h after delivery. Results

Methylergometrine was found to be superior to rest of the drugs in the study with lowest duration of third stage of labor (P = 0.000096), lowest amount of blood loss (P = 0.000017) and lowest incidence of PPH (P = 0.03). There was no significant difference in the pre-delivery and the post-delivery hemoglobin concentration amongst the four groups with P = 0.061. The need of additional oxytocics and blood transfusion was highest with misoprostol as compared to all other drugs used in the study with P = 0.037 and 0.009, respectively. As regards side effects, misoprostol was associated with shivering and pyrexia in significantly high number of patients as compared to the other drugs used in the study while nausea, vomiting and headache were more associated with methylergometrine and ergometrineoxytocin. However all the side effects were acceptable and preferable to the excessive blood loss. Conclusion Methylergometrine has the best uterotonic drug profile amongst the drugs used, strongly favouring its routine use as oxytocic for active management of third stage of labor. Misoprostol was found to cause a higher blood loss compared to other drugs and hence should be used only in low resource setting where other drugs are not available. The role of misoprostol in third stage of labor needs larger studies to be proved. Keywords: Uterotonics, 3rd stage of labor, Post-partum hemorrhage, Brass-V drapes Introduction PPH is the most serious complication in obstetric practice. The greatest number of maternal deaths from hemorrhage is due to PPH, which is almost entirely a preventable condition. PPH occurs in approximately 4% of vaginal deliveries, and estimates are that it causes significant morbidity and 25% of all the maternal child birth related deaths [1]. The WHO defines PPH as blood loss of 500 ml or more in first 24 h post partum [2]. Postpartum blood loss is difficult to evaluate especially in developing country like India where most of the women are anaemic with poor reserve and this conditions are further aggravated by increased demand during pregnancy and blood loss during 3rd stage of labor [3]. The days of expectant management, the so called hands off [4] approach seems to be over, in view of serious consequences of PPH. An attempt was hence made to study the efficacy of various oxytocics i.e. oxytocin, methylergometrine,
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syntometrine and misoprostol in reducing blood loss in active management of third stage labor, at the Department of Obstetrics and Gynecology, SSG hospital and Medical College, Baroda.

Aims and Objectives To study the effect of injection oxytocin 10 IU intramuscular, tablet misoprostol 400 gms per rectally, injection Syntometrine (0.5 mg methylergometrine + 5 IU oxytocin) intramuscular, injection methylergometrine 0.2 mg intravenously on reducing blood loss in third stage of labor, duration of third stage of labor, effect on hemoglobin of the woman, need of additional oxytocics or blood transfusion and associated side effects and complications.

Material and Method A prospective non-randomized uncontrolled clinical trial was carried out in the Department of Obstetrics and Gynecology, SSG Hospital and Medical College, Baroda from June 2007 to June 2008. Total 200 women were enrolled in the study. Women were allotted to one of the 4 groups once they fulfilled all the selection and exclusion criteria such that every 5th woman was in the same group. Active management of 3rd stage of labor was done in Group A with tablet misoprostol 400 g per rectal, Group B with injection oxytocin 10 IU intramuscular, Group C with injection methyl ergometrine 0.2 mg intravenously and Group D with injection syntometrine (methyl ergometrine 0.5 mg + oxytocin 5 IU). Women with singleton pregnancy, between 37 and 42 week of gestation, anticipated vaginal delivery, vertical lie, no high risk factors and ready to give written and informed consent were enrolled in the study. While women with hemoglobin <8 gm%, pregnancy induced hypertension, abruptioplacentae/Marginal placenta previa/lowlying, placenta, multiplepregnancy,

grandmultipara, malpresentation, polyhydramnios, previous uterine scar, chorioamnionitis, prolonged labor, intra uterine fetal death, coagulation abnormalities. History of medical disorderAsthma/epilepsy/heart or renal disease were excluded from the study. On admission to

labor room, hemoglobin and blood grouping was done. All the women were followed through the 1st and 2nd stage of labor. After this calibrated BRASS V(R) DRAPE [5] was kept under the buttocks of the patient in such a way that whatever blood used to come out was collected in the receptacle. Cord was clamped and cut immediately, and baby handed over to pediatrician. The residents avoided traction on the umbilical cord, until there was evidence of placental separation. As soon as signs of placental separation appeared the placenta was delivered by controlled cord traction. Time interval between the delivery of the baby and the placenta was noted. Duration of the 3rd stage was thus calculated. Pulse rate, temperature and blood pressure were recorded 1 h after delivery. Patient was kept in labor room under observation for a period of 2 h any complaint such as nausea, vomiting, fever, headache, chills, diarrhoea and shivering was noted. In case of marked bleeding and uterus remaining flabby, uterus was massaged and inj. PGF2 250 mg intramuscular was given. Blood transfusion given if required. Inspection of vulva for perineal tears and per-speculum examination for cervical tear was carried out and if present patients were not taken into series. A repeat hemoglobin estimation was done and 2nd postpartum day after 24 h. The statistical analysis was performed using students t test for continuous variables and the 2 and fishers exact test for categorical data. P value of <0.05 was considered statistically significant. Data were calculated as means, standard deviations (SD), numbers and frequency (%). Results The women in all the four groups were comparable as regards their age, weeks of gestation and mode of onset of labor. (Table 1).

Demographic variables of the women There was no statistically significant difference amongst the groups as regards the duration of first and second stage of labor with P value of 0.11 and 0.43, respectively for stage one and stage two of the labor, showing that the groups were comparable as regards the 1st and 2nd stage of labor. The duration of third stage of labor was significantly reduced with methylergometrine with P = 0.000096 and lowest amongst the drugs used in the study. Methylergometrine given intravenously has immediate action and hence maximum reduction in duration of 3rd stage of labor. Misoprostol given per rectally has delayed onset of action and hence longer duration of 3rd stage of labor compared to methylergometrine. A study by Bamigboye et al. [6] compared rectal misoprostol with synometrine for the management of third stage of labor and found the same results. Ng et al. [7] carried out a multicentre randomized control trial of oral misoprostol and intramuscular Syntometrine in the management of third stage of labor. There was no significant difference between the two groups in the mean blood loss, incidence of PPH and fall in hemoglobin concentration. Need of additional oxytocic was higher in misoprostol (RR = 1.62) group but manual removal of placenta was reduced (RR = 0.29). Shivering and pyrexia was more common in the misoprostol group. Sanjay rao et al. [8] compared effectiveness of tablet misoprostol 400 g orally to that of intramuscular oxytocin, 0.5 mg IV methylergometrine and 125 g of intramuscular PGF2 after the delivery of the baby. The results were compared in terms of fall in haemoglobin levels, mean duration of third stage of labor, amount of post partum
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hemorrhage and the need of additional oxytocics. The results were comparable in all the four groups. The average amount of the blood loss with the four drugs in the present study was 355, 281, 243 and 260 ml, respectively with misoprostol, oxytocin, methylergometrine and ergometrine oxytocin combination with P = 0.000017, showing that of the drugs used methylergometrine is the most effective drug in reducing the blood loss in third stage of labor. Of the drug used intravenous methylergometrine is the most effective drug in reducing the 3rd stage blood loss. The reduction in blood loss is particularly important in our country where most of child bearing population is anaemic. This reduction in blood loss reduce the incidence of post partum anaemia, infection and hence morbidity. Considering PPH as a blood loss of 500 ml, 20% patients given misoprostol developed PPH as compared with 10, 4, 6%, respectively with group B, C and D with P = 0.03 (<0.05), which is statistically significant. Thus among the four methylergometrine was found to have the lowest blood loss, strongly favouring its routine use as oxytocic for active management of third stage of labor. There was no significant difference in the pre-delivery and the post-delivery hemoglobin concentration amongst the four groups with P = 0.061. E1Rafaey et al. [9] also reported no significant differences between misoprostol and oxytocin when comparing the drop in haemoglobin concentration. This can be explained by hemodilution that occurs during pregnancy so as to compensate for the loss during pregnancy. The post partum values of haemoglobin shows variable difference in different mothers hence we calculated the percentage difference, which was also not significant. The results of our study were comparable with that of the other studies. Mcdonald and Abbott (2007-cochrane review) [10] compared effects of oxytocin with ergometrineoxytocin in reducing risk of PPH (i.e. blood loss of 500 ml) and found that ergometrineoxytocin was associated with small reduction in the risk of PPH (odds ratio = 0.82) but more of nausea, vomiting and hypertension. Parson et al. [11] compared rectal misoprostol 800 g versus oxytocin 10 IU intramuscular with delivery of anterior shoulder. The results were compared in terms of change in haemoglobin concentration before and after delivery, need of additional oxytocics, estimated blood loss, transfusion and medication side-effects. The results were comparable in both the groups.

Assessment of blood loss by visual estimation has shown to underestimate the true blood loss. A more objective method would be an assessment of the hematocrit concentration as suggested by ACOG. This is however not adopted in our study due to lack of resources. The need of additional oxytocics and blood transfusion was highest with misoprostol as compared to all other drugs used in the study with P = 0.037 and 0.009, respectively. The late absorption of rectal Misoprostol delays its effect in controlling hemorrhage during 1st hour of delivery leading to more need of oxytocic as compared to intravenous methylergometrine, which has immediate onset of action requiring rarely any additional oxytocic. Methylergometrine is associated with equal or lower blood loss as compared to oxytocin and ergometrineoxytocin in most of the studies and hence should be a preferred drug for prevention of PPH if not contraindicated. (Table 2). Hence role of misoprostol in third stage of labor needs larger studies to be proved.

There was increased frequency of headache in patients given methylergometrine and ergometrineoxytocin. Ergotamine is the most potent vasoconstrictor. The dehydrogenated amino acid alkaloids are powerful alpha-adrenergic blocking agents, hence causing headache. Methylergometrine and ergometrineoxytocin were associated with rise in blood pressure though the incidence is low and not statistically significant with P = 0.12. However, since hypertensive
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patients were not included in series, no untoward effect was seen due to this rise in blood pressure. There was higher incidence of nausea and vomiting in patients given ergometrine oxytocin and methylergometrine as compared to other drugs. Ergotamine increases peristaltic activity and can potentate the action of neostigmine on the gut and hence causing nausea and vomiting. Misoprostol caused significantly higher rate of pyrexia and shivering (P = 0.01 and 0.003) as compared to other drugs used in the study. Shivering after misoprostol is due to centrally mediated PGE1 effect associated with thermoregulatory physiology. Also the staffs were aware of the side effects leading to assessment bias. Diarrhoea was also caused more frequently with misoprostol. However the difference was not statistically significant. Lumbiganon et al. [12] report that though this may be of limited clinical concern, it can make the obstetrician suspicious of infection and cause unnecessary tests or initiation of antibiotic therapy. They also report a dose-related modest difference of 15% reduction in shivering when 400 mg is used instead of 600 mg. The advantages of the rectal route of misoprostol are less gastrointestinal side effects and advantageous especially in patients under anaesthesia and not able to tolerate orally. However, none of the side effects were life threatening or serious rather most of them subsided with 68 h post partum and very few patients actually required some treatment to alleviate them. These side effects are acceptable and preferable to excessive bleeding. Administration of the drug post-delivery should be done after proper counselling to mother regarding its side effects and their benign course (Table 3).

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Conclusion The main interest of the study was in trying to substitute intravenous methylergometrine and intramuscular oxytocin and ergometrineoxytocin with per rectal misoprostol was to avoid use of intravenous canulas and needles which is most relevant in country like ours with a high incidence of HIV infection and where use of disposable needles and IV canulas are currently unattainable. Vaginal route of misoprostol has been used for termination of pregnancy but as this route is not feasible after delivery rectal route was chosen which also has practical advantage of ease of administration in the patients who are vomiting or unable to take orally or are under anaesthesia. Amongst the four drugs oxytocin had the least side effects and maximum benefits. Rectal misoprostol is superior to oral route for limiting the side effects while maintaining the uterotonic effects and can be considered as a uterotonic for third stage of labor only if methylergometrine or oxytocin cannot be used consistently and appropriately for various reasons like drug shortage, staff not knowing intravenous/intramuscular administration, storage and refrigeration problem etc. The two major limitations of the study were, first the trial was not double blinded leading to biased results and secondly inability to eliminate the use of additional oxytocics and blood transfusion that results in a probability of masking the drop in hemoglobin concentration. Methylergometrine has the best uterotonic drug profile amongst the drugs used, strongly favouring its routine use as oxytocic for active management of third stage of labor. Misoprostol was found to cause a higher blood loss compared to other drugs and hence should be used only in low resource setting where other drugs are not available. The role of misoprostol in third stage of labor needs larger studies to be proved.

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References

1. Maughan KL, Heim SW, Galazka SS. Preventing post-partum hemorrhage: managing the third stage of labour. AAFP. 2006;73(6):10251028. 2. Fenton JJ, Baumeister LM, Fogarty J. Active management of third stage of labour among American Indian women. Fam Med. 2005;37(6):410414. [PubMed] 3. Justus Hofmeyr G, Sandra Ferreira V, Nikodem C, et al. Misoprostol for treating post partum hemorrhage: a randomized controlled trial [ISRCTN72263357] BMC Pregnancy childbirth. 2004;4:16. doi: 10.1186/1471-2393-4-16. [PMC free article] [PubMed] [Cross Ref] 4. Prendiville WJ, Elbourne D, Mc Donald S. Active versus expectant management in third stage of labour. Cochrane Database system Rev. 2000;(3):CD000007. 5. Patel A, Goudar SS, Geller SE, et al. Drape estimation vs. visual assessment for estimating postpartum hemorrhage. Int J Gynecol Obstet. 2006;95(3):312. doi: 10.1016/j.ijgo.2006.08.003. [Cross Ref] 6. Bamigboyee AA, Merell DA, Hofmeyr GI, et al. Rectal misoprostol in the prevention of postpartum hemorrhage: a placebo-controlled trial. Acta Obstet Gynecol Scand. 1998;77:178. doi: 10.1080/j.1600-0412.1998.770209.x. [PubMed] [Cross Ref] 7. Ng PS, Chan AS, Sin WK, et al. A multicentre randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of third stage of labour. Human Reprod. 2001;16(1):3135. doi: 10.1093/humrep/16.1.31. [Cross Ref] 8. Rao SB, Fonseca M, Ajmera S, et al. Is oral misoprostol a promising alternative to standard oxytocics in third stage of labour? Bombay Hosp J. 2002;44(1):3035. 9. El-Refacy H, OBrein P, Wale M, et al. Misoprostol in third stage of labour. Br J Obstet Gynecol. 1997;104:336339. doi: 10.1111/j.1471-0528.1997.tb11464.x. [Cross Ref] 10. Mac Donald SJ, Abbott JM, Higgins SP. Prophylactic ergometrine-oxytocin versus oxytocin for third stage of labour. Cochrane database of systematic reviews 2007. 11. Parsons SM, Walley RL, Crane JM, et al. Rectal misoprostol versus oxytocin in the management of third stage of labour. J Obstet Gynecol. 2007;29(9):711718.

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JURNAL Sebuah Penelitian untuk Bandingkan Efektivitas Misoprostol, Oksitosin, Methyl-ergometrine dan Ergometrin-Oksitosin dalam Mengurangi kehilangan Darah di dalam Manajemen persalinan kala 3
Disusun Guna Memenuhi Tugas dan Melengkapi Syarat Dalam Menempuh ProgramStudi Profesi Dokte

Di susun oleh : Eva apiani 030.07.086

Pembimbing : Letkol Kes dr. Zakaria, Sp. OG

RUMAH SAKIT PUSAT ANGKATAN UDARA DOKTER ESNAWAN ANTARIKSA FAKULTAS KEDOKTERAN UNIVERSITAS TRISAKTI PERIODE 3 SEPTEMBER 2012 9 NOVEMBER 2012
14

Sebuah Penelitian untuk Bandingkan Efektivitas Misoprostol, Oksitosin, Methylergometrine dan Ergometrin-Oksitosin dalam Mengurangi kehilangan Darah di dalam Manajemen persalinan kala 3

Abstrak Objektif : Tujuan dari penelitian ini adalah untuk membandingkan khasiat dari misoprostol 400 lg pre rektal, injeksi oksitosin 10 IU intramuskular, injeksi methylergometrine 0,2 mg intravena dan injeksi (0,5 mg ergometrine? 5 IU oksitosin) intramuskular dalam mengurangi hilangan darah pada kala III, durasi dari persalinan kala III, efek pada hemoglobin pasien, kebutuhan oxytocics tambahan atau transfusi darah dan hubungan dengan efek samping dan komplikasi . Desain penelitian :non-randomized uncontrolled. Penelitian dilakukan di Departemen Obstetri dan Ginekologi, SSG Hospital dan Medical College, Baroda. Terdaftar 200 wanita dan membagi mereka menjadi empat kelompok. Manajemen aktif persalinan kala 3 dilakukan dengan menggunakan salah satu dari 4 uterotonics sesuai kelompok pasien. ukuran hasil adalah jumlah kehilangan darah, kejadian perdarahan postpartum dan penurunan kadar hemoglobin dari sebelum melahirkan sampai 24 jam setelah melahirkan. Hasil: Methylergometrine terbukti lebih unggul dalam penelitian dengan durasi terendah dari persalinan kala 3 (P = 0,000096), jumlah terendah dari kehilangan darah (P = 0,000017) dan insiden terendah PPP (P = 0,03). Tidak ada perbedaan kadar hemoglobin yang signifikan sebelum persalinan dan sesudah persalinan diantara empat kelompok dengan P = 0,061. Kebutuhan oxytocics tambahan dan transfusi darah adalah tertinggi dengan misoprostol dibandingkan dengan semua obat lain yang digunakan dalam penelitian dengan P = 0,037 dan 0,009 masing-masing. Mengenai efek samping misoprostol berkaitan dengan cukup tingginya jumlah pasien yang menggigil dan demam dibandingkan dengan obat lain yang digunakan dalam penelitian. sementara mual, muntah dan sakit kepala yang lebih terkait dengan methylergometrine dan ergometrine-oksitosin. Namun semua efek samping masih dapat diterima dan lebih baik daripada kehilangan darah yang berlebihan.

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Kesimpulan : Methylergometrine merupakan obat uterotonika terbaik di antara obat-obatan lain yang digunakan, sangat mendukung untuk digunakan rutin sebagai oksitosik untuk manajemen aktif persalinan kala 3. Misoprostol terbukti menyebabkan kehilangan darah lebih tinggi dibandingkan dengan obat lain dan karenanya harus hanya digunakan dalam sumber daya yang rendah di mana obat lain tidak tersedia. Peran misoprostol di persalinan kala 3 membutuhkan penelitian yang lebih besar harus dibuktikan. Pengantar PPP merupakan komplikasi yang paling serius dalam praktek kebidanan. Sebagian besar kematian ibu akibat perdarahan yang disebabkan PPP, yang hampir seluruhnya merupakan kondisi yang dapat dicegah. PPP terjadi pada sekitar 4% dari persalinan vagina, dan di perkiraan bahwa hal itu menyebabkan morbiditas yang signifikan dan 25% dari semua kelahiran anak ibu terkait kematian [1]. WHO mendefinisikan PPP sebagai kehilangan darah 500 ml atau lebih dalam 24 jam pertama post partum
[2].

kehilangan darah Postpartum sulit untuk di evaluasi terutama di

negara berkembang seperti India di mana sebagian besar wanita mengalami anemia dengan miskin cadangan dan kondisi ini semakin diperparah oleh peningkatan kebutuhan selama kehamilan dan kehilangan darah selama persalinan kala 3 disebut'' hands off''
[4] [3].

Hari-hari manajemen hamil,yang

Pendekatan ini tampaknya lebih, melihat konsekuensi serius dari

PPP.Maka suatu usaha dibuat untuk mempelajari efektifitas dari berbagai oxytocics misalnya oksitosin, methylergometrine, syntometrine dan misoprostoldalam mengurangi hilangannya darah dalam pengelolaan aktif persalinan kala 3 , di Departemen Obstetri dan Ginekologi,SSG rumah sakit dan Medical College, Baroda.

Maksud dan Tujuan Untuk mempelajari pengaruh injeksi oksitosin 10 IU intramuskular, tablet misoprostol 400 lgms per rektal, injeksi Syntometrine (0,5 mg methylergometrine 5 IU? Oksitosin) intramuskular, injeksi methylergometrine 0,2 mg intravena dalam mengurangi kehilangan darah dalam persalinan kala 3, lama durasi dari kala 3, efek pada hemoglobin wanita, kebutuhan oxytocics tambahan atau transfusi darah dan hubungan efek samping dan komplikasi.

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Bahan dan Metode Sebuah uji klinis prospektif terkontrol non-acak dilakukan di Departemen Obstetri dan Ginekologi, SSG Hospital dan Medical College, Baroda dari Juni 2007 sampai Juni 2008. Total 200 perempuan yang di ikutsertakan dalam penelitian. Perempuan yang dialokasikan untuk salah satu dari 4 kelompok setelah mereka memenuhi semua seleksi dan eksklusi. Kriteria sehingga setiap wanita 5th berada di kelompok yang sama. Manajemen aktif persalinan kala 3 dilakukan di Grup A dengan tablet misoprostol 400 lg per rektal, Grup B dengan injeksi oksitosin 10 IU intramuskular, Grup C dengan injeksi mg ergometrine metil 0,2 intravena dan Grup D dengan injeksi syntometrine (metil ergometrine 0,5 mg? oksitosin 5 IU). Wanita dengan kehamilan tunggal, usia kehamilan antara 37 dan 42 minggu , diantisipasi persalinan pervagina , tidak ada faktor risiko tinggi dan siap untuk memberikan keterangan dan informed consent sudah terdaftar dalam penelitian ini. sementara wanita dengan hemoglobin 8 gm%, hipertensi kehamilan diinduksi, solusio placentae / Marginal plasenta previa , lowlying plasenta, kehamilan ganda, grand multipara, malpresentation,polihidramnion, bekas luka di rahim sebelumnya, korioamnionitis, kematian janin intra uterin, kelainan koagulasi. Riwayat gangguan-medis Asma / epilepsi / penyakit jantung atau ginjal dikecualikan dari penelitian. Masuk ke ruang bersalin, pengelompokan hemoglobin dan darah dilakukan. Semua perempuan Diikuti dari persalinan kala 1 dan kala 2 . Setelah ini dikalibrasiBRASS V(R) DRAPE
[5]

disimpan di bawah pantat pasien, sedemikian rupa sehingga apapun darah yang digunakan dikumpulkan dalam wadah tersebut. plasenta segera dijepit dan dipotong, bayi diserahkan kepada dokter anak. Warga menghindari tarikan pada tali pusat, Sampai Ada bukti pemisahan plasenta. Segera setelah tanda-tanda pemisahan plasenta Muncul, plasenta dilahirkan dengan tarikan tali pusat terkendali. interval waktu Antara lahir bayi dan plasenta telah di catat. Durasi dari kala 3 telah hitung. tingkat, nadi , suhu dan tekanan darah telah tercatat 1 jam setelah melahirkan. Pasien tetap berada di ruang bersalin dan di observasi selama 2 jam. Keluhan Seperti mual, muntah, demam, sakit kepala, menggigil, Diare dan menggigil diperhatikan. Dalam kasus yang di tandai dengan perdarahan dan rahimtersisa lembek, uterus dipijat dan di berikan inj. PGF2a250 mg intramuskular. Transfusi darah diberikan bila diperlukan. Pemeriksaan vulva untuk robekan perineum dan pemeriksaan perspeculum

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untuk robekan serviks dilakukan jika ada di pasein maka tidak dimasukan ke dalam seri. Estimasi ulangi hemoglobin ke 2 post partum setelah 24 jam. Statistik analisis ini dilakukan menggunakan test siswa untuk terus-menerus variabel dan v2 dan fisher tepat tes untuk data kategoris. Nilai P \0.05 dianggap signifikan secara statistik. Data dihitung sebagai berarti, deviasi standar (SD), nomor, dan frekuensi (%).

Hasil Semua Perempuan dalam empat kelompok adalah sebanding dalam hal usia mereka, usia kehamilan dan mode onset persalinan. (Tabel 1). Tidak ada perbedaan yang signifikan secara statistik antara grup mengenai durasi persalinan kala 1 dan kala 2 dengan nilai P 0,11 dan 0,43, masing-masing untuk persalinan kala 1 dan kala 2 , menunjukkan bahwa semua kelompok sebanding dalam hal persalinan kala 1 dan kala 2 . Durasi persalinan ala 3 secara signifikan berkurang dengan methylergometrine P = 0.000096 dan merupakan yang terendah di antara obatobatan lain yang digunakan dalam penelitian. Methylergometrineyang diberikan intravena memiliki efek segera oleh karna itu terdapat penurunan maksimum dalam durasi kala 3 persalinan.

Misoprostol yang diberikan prerectal memiliki onset tindakan yang lama dan karenanya durasi yang lebih lama dari persalinan kala 3 dibandingkan untuk methylergometrine. Sebuah studi oleh Bamigboye et al. [6] membandingkan misoprostol per rectal dengan synometrine dalam manajemen kala 3 persalinan dan menemukan hasil yang sama. Ng et al. [7] Melakukan uji coba acak multisenter secara terkontrol mengenai misoprostol oral dan Syntometrine
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intramuskular dalam pengelolaan kala 3 persalinan . Tidak ada perbedaan yang signifikan antara kedua kelompok dalam rata-rata kehilangan darah, kejadian PPP dan konsentrasi hemoglobin. Kebutuhan tambahan oxytocic lebih tinggi pada kelompok misoprostol (RR = 1,62) tapi pengangkatan plasenta secara manual berkurang (RR = 0,29). Menggigil dan pireksia adalah lebih umum pada kelompok misoprostol. Sanjay Rao et al. [8] membandingkan efektivitas misoprostol 400 oral dengan oksitosin intramuskular , 0,5 mg IV Methylergometrine dan 125 lg intramuskular PGF2a setelah melahirkan bayi. Hasil Dibandingkan dalam penurunan kadar hemoglobin, durasi persalinan kala 3, jumlah perdarahan postpartum dan kebutuhan oxytocics tambahan. Hasil sebanding di semua empat kelompok. Jumlah rata-rata kehilangan darah dengan ke empat obat-obatan dalam studi adalah 355, 281, 243 dan 260 ml, berturut-turut mulai dari misoprostol, oxytosin, methylergometrine dan kombinasi ergometrineoxytocin dengan P = 0.000017, menunjukkan bahwa methylergometrine adalah obat yang paling efektif dalam mengurangi kehilangan darah dalam kala 3 persalinan. methylergometrine intravena merupakan obat yang paling efektif dalam mengurangi kehilangan darah di kala 3 persalinan. Pengurangan kehilangan darah sangat penting di negara kita yang mana sebagian besar penduduk anemia. Pengurangan kehilangan darah mengurangi timbulnya post partum anemia, infeksi dan morbiditas. Mengingat PPP sebagai kehilangan darah C500 ml, 20% pasien yang diberikan misoprostol berkembang menjadi PPP dibandingkan dengan 10, 4, 6%, masing-masing dengan Grup B, C dan D dengan P = 0,03 (\0.05), yang merupakan signifikan secara statistik. Dengan demikian antara empat methylergometrine ditemukan memiliki kehilangan darah yang terendah, sangat menguntungkan penggunaannya sebagai oxytocic rutin untuk manajemen aktif kala 3 persalinan . Ada tidak ada perbedaan yang signifikan dalam konsentrasi hemoglobi predelivery dan post-delivery di antara empat kelompok dengan P = 0.061. E1Rafaey et al. [9] juga melaporkan tidak ada perbedaan yang signifikan antara misoprostol dan oxytosin ketika membandingkan penurunan konsentrasi hemoglobin . Hal ini dapat dijelaskan oleh hemodilution yang terjadi selama kehamilan untuk mengkompensasi kerugian selama kehamilan. nilai hemoglobin post partum menunjukkan perbedaan variabel pada ibu yang berbeda karna itu kita menghitung perbedaan persentase, yang juga tidak signifikan. Hasil studi kami yang sebanding dengan studi yang lain. McDonald dan Abbott (2007-cochrane review) [10] membandingkan efek oxytosin dengan ergometrineoxytocin dalam mengurangi risiko PPP (yaitu kehilangan 500
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ml darah) dan menemukan bahwa ergometrineoxytocin berkaitan dengan penurunan risiko PPH (rasio peluang = 0.82) tetapi lebih mual, muntah, dan hipertensi. Parson et al. [11] dibandingkan misoprostol 800 lg pre rectal dengan oxytosin 10 IU intramuskular dalam persalinan bahu anterior . Hasil yang dibandingkan dalam hal perubahan dalam konsentrasi hemoglobin sebelum dan sesudah persalinan, membutuhkan tambahan oxytocics, diperkirakan kehilangan darah , transfusi dan efek samping obat . Hasil yang sebanding dalam kedua group. Penilaian kehilangan darah dengan estimasi visual telah ditunjukan untuk meremehkan kehilangan darah yang benarnya. Sebuah metode yang lebih obyektif akan menilai konsentrasi hematokrit sebagaimana disarankan oleh ACOG. Namun hal ini tidak dilakukan dalam penelitian kami karena Kurangnya sumber daya. Kebutuhan oxytocics tambahan dan transfusi darah yang tertinggi adalah dengan Misoprostol seperti Dibandingkan dengan semua obat lain yang digunakan dalam penelitian dengan P = 0,037 dan 0,009 masing-masing. Penyerapan yang lambat dari Misoprostol prerectal berefek dalam pegendalian perdarahan Selama 1 jam persalinan mengarah ke kebutuhan lebih oxytocic sebagai Dibandingkan dengan

Methylergometrine intravena, Yang memiliki onset langsung dan jarang membutuhkan oxytocic tambahan . Methylergometrine terkait kehilangan Darah adalah sama atau lebih rendah Dibandingkan dengan oksitosin dan Ergometrin-oksitosin dikebanyakan penelitian dan

karenanya harus menjadi obat pilihan untuk pencegahan PPP jika tidak kontraindikasi. (Tabel 2). Oleh karena itu peran misoprostol dalam kala 3 persalinan memburtuhkan penelitian yang lebih besar.

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Ada Peningkatan frekuensi sakit kepala pada pasien yang diberikan Methylergometrine dan Ergometrin-oksitosin. Ergotamine adalah vasokonstriktor kuat. The dehydrogenated amino acid alkaloids adalah agen bloking alpha adrenergic yang kuat oleh karena itu menyebabkan sakit kepala. Methylergometrine dan Ergometrin-oksitosin terkait dengan peningkatan tekanan darah meskipun Insidennya rendah dan tidak signifikan secara statistik dengan p = 0,12. Namun, karena pasien hipertensi tidak dimasuk ke dalam seri, tidak ada efek yang tak diinginkan terlihat karena hal ini menyebabkan kenaikan tekanan darah. Insiden mual dan muntah pada pasien yang di berikan Ergometrin-oksitosin dan Methylergometrine lebih tinggi bila dibandingkan dengan obat lain. Ergotamine meningkatkan aktivitas peristaltik dan potensial aksi dari neostigmine pada usus dan karenanya menyebabkan mual muntah. Misoprostol Secara signifikan menyebabkan pireksia dan menggigil lebih tinggi tingkat (P = 0,01 dan 0,003) bila dibandingkan dengan obat lain yang digunakan dalam penelitian ini. Menggigil setelah misoprostol adalah karena pusat PGE1 dimediasi efeknya terkait dengan fisiologi thermoregulatory. Para staf juga menyadari efek samping yang mengarah bias penilaian. Diare juga lebih sering pada pemberian Misoprostol. Namun Perbedaan itu tidak signifikan secara statistik. Lumbiganon et al. [12] melaporkan hal tersebut meskipun klinis ini Mungkin terbatas pada kekhawatiran, hal itu dapat membuat dokter kandungan mencurigai adanya infeksi dan menyebabkan tes yang tidak perlu atau inisiasi terapi antibiotik Mereka Juga elaporkan perbedaan yang berhubungan dengan dosis, pengurangan menggigil sebnyak 15% Ketika 400 mg digunakan sebagai pengganti dari 600 mg. Keuntungan dari rute rektal misoprostol adalah sedikit efek samping pada

gastrointestinal,terutama pada pasien di bawah anestesi dan tidak Mampu melakukan secara oral. Namun, tidak ada efek samping yang serius atau mengancam kehidupan. kebanyakan mereka mereda setelah 6-8 jam post partum dan sangat sedikit pasien yang memerlukan beberapa perawatan untuk meringankan keluhan tersebut. Efek ini dapat diterima dan lebih disukai daripada perdarahan yang berlebihan. Administrasi pemeberian obat pasca-persalinan harus dilakukan untuk ibu setelah konseling yang tepat Mengenai efek sampingnya dan mereka jinak saja (Tabel 3).

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Kesimpulan Kepentingan utama dalam studi ini adalah mencoba untuk menggantikan methylergometrine intravena dan oxytosin intramuskular dan ergometrineoxytocin dengan misoprostol pre rectal untuk menghindari penggunaan canulas intravena dan jarum yang mana paling relevan di negara seperti kita dengan tingginya insiden infeksi HIV dan di mana menggunakan jarum sekali pakai dan IV canulas saat ini tak terjangkau. Vagina rute misoprostol telah digunakan untuk penghentian kehamilan tetapi rute ini tidak layak setelah persalinan, pre rectal dipilih yang juga karena praktis, memiliki keuntungan dan kemudahan administrasi pada pasien yang muntah atau tidak dapat di minum peroral atau di bawah anestesi.Di antara empat obat, oksitosin memiliki efek samping yang sedikit dan manfaat yang maksimal. Misoprostol prerektal lebih unggul rute oral untuk Membatasi efek samping sementara Mempertahankan efek uterotonika dan dapat dianggap sebagai uterotonika untuk kala 3 persalinan hanya jika Methylergometrine atau oxytocin tidak dapat digunakan secara konsisten dan untuk berbagai alasan yang tepat seperti kekurangan obat, staf tidak tahu pengunaan intravena / intramuskular, masalah penyimpanan dan pendingin, dll. Dua Keterbatasan utama dalam penelitian adalah, pertama percobaan tidak double blinded sehingga mengarah ke hasil yang bias dan kedua ketidakmampuan untuk menghilangkan penggunaan oxytocics tambahan dan transfusi darah yang menghasilkan kemungkinan tertutupnya penurunan kadar hemoglobin. Methylergometrine memiliki profil obat uterotonic
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terbaik antara obat-obatan yang digunakan, yang sangat menguntungkan penggunaannya rutin sebagai oxytocic untuk aktif manajemen kala 3 persalinan Misoprostol telah dibuktikan menyebabkan kehilangan darah lebih tinggi dibandingkan dengan obat lain dan karenanya harus digunakan jika dalam sumberdaya yang kurang dimana obat lain tidak tersedia. Peran misoprostol dalam kala 3 persalinan membutuhkan penelitian yang lebih besar untuk dibuktikan.

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Daftar pustaka

1. Maughan KL, Heim SW, Galazka SS. Preventing post-partum hemorrhage: managing the third stage of labour. AAFP. 2006;73(6):10258. 2. Fenton JJ, Baumeister LM, Fogarty J. Active management of third stage of labour among American Indian women. Fam Med. 2005;37(6):4104. 3. Justus Hofmeyr G, Sandra Ferreira V, Nikodem C, et al. Misoprostol for treating post partum hemorrhage: a randomized controlled trial [ISRCTN72263357]. BMC Pregnancy childbirth. 2004;4:16. 4. Prendiville WJ, Elbourne D, Mc Donald S. Active versus expectant management in third stage of labour. Cochrane Database system Rev. 2000;(3):CD000007. 5. Patel A, Goudar SS, Geller SE, et al. Drape estimation vs. visual assessment for estimating postpartum hemorrhage. Int J Gynecol Obstet. 2006;95(3):312. 6. Bamigboyee AA, Merell DA, Hofmeyr GI, et al. Rectal misoprostol in the prevention of postpartum hemorrhage: a placebocontrolled trial. Acta Obstet Gynecol Scand. 1998;77:178. 7. Ng PS, Chan AS, Sin WK, et al. A multicentre randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of third stage of labour. Human Reprod. 1. 2001;16(1):315. 8. Rao SB, Fonseca M, Ajmera S, et al. Is oral misoprostol a promising alternative to standard oxytocics in third stage of labour? Bombay Hosp J. 2002;44(1):305. 9. El-Refacy H, OBrein P, Wale M, et al. Misoprostol in third stage of labour. Br J Obstet Gynecol. 1997;104:3369. 10. Mac Donald SJ, Abbott JM, Higgins SP. Prophylactic ergometrine- oxytocin versus oxytocin for third stage of labour. Cochrane database of systematic reviews 2007. 11. Parsons SM, Walley RL, Crane JM, et al. Rectal misoprostol versus oxytocin in the management of third stage of labour. J Obstet Gynecol. 2007;29(9):7118.

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