|Year : 2022 | Volume
| Issue : 2 | Page : 124-128
Comparison of sublingual misoprostol with intramuscular oxytocin in active management of the third stage of labor
Harsha Charaya, Monica Soni, Jeevika Gupta, Asmita Nayak
Department of Obstetrics and Gynaecology, SP Medical College, Bikaner, Rajasthan, India
|Date of Submission||04-May-2022|
|Date of Decision||02-Aug-2022|
|Date of Acceptance||04-Aug-2022|
|Date of Web Publication||23-Dec-2022|
Department of Obstetrics and Gynaecology, SP Medical College, Bikaner, Rajasthan
Source of Support: None, Conflict of Interest: None
Background: Postpartum hemorrhage (PPH) is the most common cause of maternal mortality worldwide. Significant numbers are preventable, especially in low-resource settings. Active management of the third stage of labor (AMTSL) is a key denominator. The present study aimed to compare sublingual misoprostol with intramuscular oxytocin in AMTSL to search for an easy and effective alternative for low-resource settings.
Materials and Methods: A prospective randomized comparative study was conducted, where the subjects were registered over 1 year extending from May 2020 to June 2021 including 200 patients admitted to the labor room with term pregnancy with a period of gestation between 37 and 42 weeks and were divided into two groups, Group A and Group B receiving intramuscular oxytocin and sublingual misoprostol, respectively.
Results: Sublingual misoprostol was equally effective compared with intramuscular oxytocin in the prevention of PPH. There were no statistical differences in the duration of the third stage of labor, need for additional uterotonics, need for manual removal of placenta, and need for blood transfusion in the two groups.
Conclusion: Sublingual misoprostol appeared to be as effective as intramuscular oxytocin in the AMTSL and may be an alternative, especially in low-resource settings.
Keywords: Active management of the third stage of labor, misoprostol, oxytocin
|How to cite this article:|
Charaya H, Soni M, Gupta J, Nayak A. Comparison of sublingual misoprostol with intramuscular oxytocin in active management of the third stage of labor. J Curr Res Sci Med 2022;8:124-8
|How to cite this URL:|
Charaya H, Soni M, Gupta J, Nayak A. Comparison of sublingual misoprostol with intramuscular oxytocin in active management of the third stage of labor. J Curr Res Sci Med [serial online] 2022 [cited 2023 Mar 20];8:124-8. Available from: https://www.jcrsmed.org/text.asp?2022/8/2/124/364498
| Introduction|| |
Misoprostol first came into use for the prevention of peptic ulcer disease, was also found useful for termination of pregnancy, and then as a miracle drug in the prevention of postpartum hemorrhage (PPH). However, the drug which is being used for this purpose universally is oxytocin for almost half a decade after being introduced in 1963 at the National Maternity Hospital in Dublin, Ireland. The World Health Organization (WHO) reports that almost 800 women die every day because of pregnancy- or childbirth-related complications around the world. PPH is the leading cause of maternal mortality globally accounting for approximately 25% of maternal deaths., Although potentially life-threatening, albeit it is preventable. PPH occurs mostly during the third stage of labor which is defined as the time from the delivery of the baby to the expulsion of the placenta and its membranes. Physiological or expectant management of the third stage of labor involves waiting for signs of separation of the placenta and allowing the placenta to deliver spontaneously or aided by nipple stimulation or gravity (WHO, 2012). Active management of the third stage of labor (AMTSL) means expediting the process by early cord clamping, administration of an uterotonic, delivery of placenta by controlled cord traction following uterine contraction, and finally uterine massage after delivery of the complete placenta. Uterotonics play a pivotal role to decrease postpartum blood loss and thus form an important component of AMTSL. The use of oxytocin in the AMTSL is fraught with problems of storage, fake and substandard drugs, and the need for trained staff to administer it. Misoprostol, on the other hand, offers several advantages over oxytocin. In resource-poor countries, poor geographic access, inadequate infrastructure, and lack of a qualified provider or injectable oxytocin requiring storage in a refrigerator can preclude its use as prophylactic uterotonic, especially in home birth settings where oral misoprostol could be a reasonable alternative. Based on this framework, the present study was carried out to compare the efficacy and safety of oral misoprostol with intramuscular oxytocin in the AMTSL.
| Materials and Methods|| |
This prospective randomized comparative study was conducted including 200 cases registered over 1 year extending from May 2020 to June 2021 screened from patients admitted to the labor room with term pregnancy with a period of gestation between 37 and 42 weeks. After obtaining due approval from the Institutional Ethics Board (5815 approval no.) and written and informed consent of participants, 200 participants were recruited for the study after screening for inclusion and exclusion criteria. Patients with age 19–35 years, 37–42 weeks of gestation, singleton pregnancy, vertex presentation, and low parity (≤3) were included in the study. Patients with previous cesarean section, multiple pregnancies, breech presentation, multipara >3, instrumental deliveries, intrauterine fetal death, previously scarred uterus (myomectomy/hysterotomy), and other severe diseases of cardiac/renal/hepatic/epileptic/severe pregnancy induced hypertension (PIH)/severe anemia were excluded.
The study was participant blinded and unstratified randomization was done using an open list of the computer-generated random number chosen by the participant. The random number was mentioned on the patient's file. Two groups were made.
Group A: One hundred patients were enrolled in Group A who were given I. M. oxytocin 10 U after delivery of the anterior shoulder of the baby.
Group B: One hundred patients were enrolled in Group B who were given sublingual misoprostol 600 mcg after delivery of the anterior shoulder of the baby.
Hemoglobin (Hb) levels, duration of the third stage of labor, amount of third-stage blood loss according to the equation given below, blood pressure 1 and 5 min after drug delivery, and side effects of the drugs were observed and noted. Requisition of additional uterotonics and blood components in either group was noted.
The equation used for blood loss soaked items was: Wet item weight (in grams) – dry item weight (in grams) = ml of blood in item.
One gram = One milliliter of blood volume loss.
| Results|| |
The two groups were comparable at randomization for potentially confounding factors such as age, booking status, and gestational age at delivery. The two groups were also comparable in baseline prognostic labor characteristics such as duration of labor and mode of delivery. The mean age of patients in Group A was 24.4 ± 4.47 years while that in Group B was 25.13 ± 4.5 years with a statistically insignificant difference. The mean duration of the third stage of labor was 3.4 ± 1.9 min in Group A and 3.6 ± 1.8 min in Group B. With a T score of 0.76 and P = 0.44, the difference in the mean duration of the third stage of labor was statistically insignificant [Table 1]. The mean blood loss during the third stage was 144.25 ± 82.91 ml in study Group A and 163.37 ± 86.82 ml in Group B. The amount of blood loss was higher in Group B, but the difference was statistically insignificant [T score = 1.59; P = 0.11, [Table 2]]. The mean Hb level before delivery was 10.42 ± 2.12 g/dl (range from 7 to 14.3 g/dl) in study Group A and 10.35 ± 2.01 g/dl (range from 6.8 to 14.1 g/dl) in Group B, and the difference was statistically insignificant (P = 0.81). The mean Hb level after delivery was 9.83 ± 1.97 g/dl (range from 6.9 to 13.7 g/dl) in study Group A and 8.96 ± 1.64 g/dl (range from 5.8 to 13.5 g/dl) in Group B. Postdelivery, the mean hemoglobin level was lower in Group B, but the difference was statistically insignificant [P = 0.29, [Table 3]]. The incidence of PPH in Group A was 3% whereas, in Group B, 2% of patients experienced PPH. The incidence of third-stage complications was comparable in the two groups [P = 0.44, [Table 4]]. In Group A, the incidence of nausea was 22%, headache was 5%, vomiting was 5%, and shivering was 4%. In addition, 1% of the patients developed transient hypertension. In Group B, the incidence of nausea was 28%, headache was 16%, vomiting was 20% and shivering was 4%. There was a highly significant difference in the incidence of adverse events between the two groups (P = 0.003) with Group B having a higher incidence of adverse events [Figure 1]. In Group A, only 7 cases needed additional uterotonics such as misoprostol (5 cases) and Methergine (2 cases). In Group B, 11 patients required additional uterotonic in the form of oxytocin 10 units IV infusion, and 3 patients required Methergine. The need for additional uterotonics was statistically similar in the two groups [P = 0.44, [Figure 2]].
|Table 3: Distribution of cases according to their postdelivery hemoglobin level (g/dL)|
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|Figure 1: Distribution of cases according to systemic side effects of drugs|
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| Discussion|| |
Misoprostol in AMTSL has been reported to effectively reduce the incidence of primary PPH from 18% to 5%. In addition, the time for administration of therapeutic drugs is reduced from 15 to 5 min. This practice has become a standard of obstetric care, and misoprostol has emerged as a promising treatment substitute.,,
This prospective randomized comparative study was conducted in the department of obstetrics and gynecology, at a tertiary care hospital, extending over 1 year from May 2020 to June 2021 to evaluate the efficacy and safety of 600 μg sublingual misoprostol with intramuscular oxytocin 10 units administered during the third stage of labor after delivery of anterior shoulder of the baby.
In our study, the maximum number of cases was between 21 and 25 years of age in both the groups [Table 1]. While 44% of women belonged to this age group in Group A, 42% in Group B were from this age group. The mean age of patients in Group A was 24.4 ± 4.47 years while that in Group B was 25.13 ± 4.5 years which was comparable between the two groups (P = 0.25) with an insignificant difference statistically. Subedi et al. (2018) in their study found the mean age in the oxytocin group to be 24.28 ± 4.49 years and 23.3 ± 3.37 years in the misoprostol group.
In Group A, 58% of the patients and, in Group B, 55% of the patients were from rural areas. Forty-two percent of patients in Group A and 45% of patients in Group B were from urban areas. Regarding residence, the two groups were comparable with P = 0.67. A higher percentage of women living in rural areas get formerly married compared with women in urban areas or nonmetropolitan cities, thus accounting for a higher number of cases from rural backgrounds. Knowledge gaps about contraception and lack of access to health-care providers or services for the same play a significant role in this disparity. Among Group A, spontaneous onset of labor was reported in 82% and induced labor in 18% of patients, while in Group B, 84% had spontaneous onset of labor and 16% of cases went for induction of labor (P = 0.71). There was a statistically insignificant difference in the onset of labor between the two groups.
Duration of the third stage of labor
In our study, the duration of the third stage of labor for most of the mothers was <10 min. Thirty-three percent of cases in Group A and 29% of cases in Group B had a duration of the third stage of labor <2 min. The mean duration of the third stage of labor was 3.4 ± 1.9 min in Group A and 3.6 ± 1.8 min in Group B, and the difference was statistically insignificant with P = 0.44. Elaty et al. found that the mean duration of the third stage of labor in Group A treated with oxytocin was 3.35 ± 1.62 min and 3.38 ± 1.76 min in Group B treated with misoprostol. With P = 0.823, they found the difference to be statistically insignificant. Tewatia et al. in their study had a third-stage duration lasting <5 min with median durations between 5 and 5.37 min with oxytocin and 5.23 and 5.5 min with misoprostol. Aziz et al. in their study in 2014 comparing oxytocin 10 units intramuscular and oral misoprostol 600 μg found that the mean duration of the third stage of labor was 5.23 ± 2.46 min in the misoprostol group and 5.23 ± 2.46 min in oxytocin group.
Third-stage blood loss
In our study, maximum cases had blood loss in the range of 100–150 ml in both the groups, 39% and 34% in Group A and Group B, respectively. The mean blood loss during the third stage of labor was 144.25 ± 82.91 ml in study Group A and 163.37 ± 86.82 ml in Group B (P = 0.11). Only 4% and 2% of cases had blood loss >300 ml in Groups A and B, respectively. A majority of cases (39% in Group A and 34% in Group B) had blood loss of <100 ml. Kundodyiwa et al. found a statistically insignificant difference in the amount of third-stage blood loss between the two groups (misoprostol versus oxytocin; 354 and 348 ml, respectively). Nordstrom et al. reported the amount of blood loss >500 ml in 9% of cases managed with misoprostol and 9.3% of cases given oxytocin.
Aziz et al. reported the average amount of blood loss to be higher in the group treated with misoprostol (302.86 ± 160.4 ml) than oxytocin (267.14 ± 140.35 ml) with significant P = 0.236.
Differences in hemoglobin and hematocrit
Changes in hematological parameters, namely fall in Hb level following delivery, can be taken as a reliable method for blood loss assessment during delivery. On comparing the postdelivery Hb and predelivery Hb levels, a fall in Hb level was observed in the women of both the groups in our study. The mean Hb level before delivery was 10.42 ± 2.12 g/dl (range from 7 to 14.3 g/dl) in study Group A and 10.35 ± 2.01 g/dl (range from 6.8 to 14.1 g/dl) in Group B (P = 0.81). The mean Hb level after delivery was 9.83 ± 1.97 g/dl (range from 8.9 to 13.7 g/dl) in study Group A and 8.96 ± 1.64 g/dl (range from 8.8 to 13.5 g/dl) in Group B (P = 0.29). The two groups were comparable in predelivery mean Hb level. Postdelivery and fall in mean Hb level were higher in Group B, but the difference was statistically insignificant. The mean fall in predelivery and postdelivery Hb levels was 1.09 ± 0.81 g/dl (range from 0.3 to 2.2 g/dl) in study Group A and 2.12 ± 0.59 g/dl (range from 0.3 to 2.8 g/dl) in Group B. The mean fall in Hb was statistically insignificant between the two groups (P = 0.06).
Basket et al. found that the mean Hb fall after delivery was 0.34 ± 0.35 g/dl in oxytocin and 0.33 ± 0.38 g/dl in the misoprostol group. The difference was statistically insignificant. There was also no significant difference between the two groups regarding the drop in hematocrit (a ≥10% hematocrit drop occurred in 3.4% and 3.7% of the participants in the oxytocin and misoprostol groups, respectively; P = 0.98).
Nagashree et al. found that there was a statistically significant difference between the postdelivery mean Hb values of the 800 μg rectal misoprostol group versus the intravenous oxytocin (5 IU) group (P = 0.87). Evaluated 200 μg of rectal misoprostol and 20 IU intravenous oxytocin groups in terms of the changes in the values of hematocrit, but no statistically significant difference was observed (P = 0.28).
| Conclusion|| |
In our study, it was found that oral misoprostol, as a prophylactic uterotonic, was as effective as intramuscular oxytocin in AMTSL with a slightly higher incidence of side effects. Globally, maternal mortality is unacceptably high and the majority of these (94%) occur in low-resource settings and are preventable. The most common cause worldwide is PPH. In developing countries, the burden of PPH can be significantly alleviated through prophylactic administration of uterotonic in AMTSL. In low-resource settings, where resource constraints in terms of infrastructure and trained health-care personnel and climatic conditions can preclude the utilization of the heat-labile intramuscular oxytocin preparations, misoprostol, being sustainable, stable, and easy to administer, should be considered for use in AMTSL. Further larger trials implementing its use as a first-line agent in AMTSL are needed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]