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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 3  |  Page : 1189-1194

Comparison between preoperative sublingual and rectal misoprostol on blood loss in elective cesarean delivery


Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission12-Jan-2021
Date of Decision24-Feb-2021
Date of Acceptance02-Mar-2021
Date of Web Publication18-Oct-2021

Correspondence Address:
Rania E. Mohammad Abdul Gawwad
38(A), Kamal Hijab st, Ain Shams, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_11_21

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  Abstract 


Objectives
To compare between the effect of preoperative sublingual versus rectal misoprostol on blood loss during and after elective cesarean section.
Background
Cesarean delivery is the commonest major women's surgery worldwide. Postpartum hemorrhage is a major cause of maternal mortality, mainly in developing countries. Misoprostol is one of the synthetic PGE1 analogs with strong uterotonic activity.
Patients and methods
This randomized controlled clinical trial was conducted in the Obstetrics and Gynecology Department, Faculty of Medicine, Menoufia University Hospital, in the period from September 2019 to July 2020. The study included 135 term pregnant women randomized into three equal groups (rectal, sublingual, and control). Full history, general examination, obstetric examination, routine investigation, and obstetrics ultrasound were done. All participants underwent elective cesarean delivery under spinal anesthesia. The patient was catheterized then the rectal or sublingual misoprostol tablets (400 μg) were administered according to a randomization plan. All cases received 10 IU of oxytocin by slow intravenous injection after cord clamping.
Results
Intraoperative blood loss was lowest in sublingual group (352.5 ± 116.91) followed by rectal group (438.2 ± 190.19) and was highest in control group (621.2 ± 207.25). Postoperative hematocrit was lowest in the control group (33 ± 3.44) followed by the rectal group (35.09 ± 4.58) and was highest in the sublingual group (35.5 ± 3.46).
Conclusion
Misoprostol with oxytocin is an effective drug combination to prevent postpartum hemorrhage and decrease intraoperative blood loss during cesarean section with better results through sublingual than rectal route.

Keywords: cesarean delivery, misoprostol, postpartum hemorrhage, rectal, sublingual


How to cite this article:
Hosni NM, Abd El-Aal NK, Gawwad RE, Anter ME. Comparison between preoperative sublingual and rectal misoprostol on blood loss in elective cesarean delivery. Menoufia Med J 2021;34:1189-94

How to cite this URL:
Hosni NM, Abd El-Aal NK, Gawwad RE, Anter ME. Comparison between preoperative sublingual and rectal misoprostol on blood loss in elective cesarean delivery. Menoufia Med J [serial online] 2021 [cited 2024 Mar 29];34:1189-94. Available from: http://www.mmj.eg.net/text.asp?2021/34/3/1189/328288




  Introduction Top


Cesarean delivery is the commonest major women's surgery worldwide [1]. The incidence ranges from 20 to 30% all over the world [2]. In 2017, the ACOG changed the classic definition of postpartum hemorrhage (PPH) to be defined as loss of cumulative blood loss more than or equal to 1000 ml, or bleeding associated with signs/symptoms of hypovolemia within 24 h of the birth process regardless of delivery route. PPH is also defined as bleeding that is greater than expected, more than 1% of bodyweight, resulting in drop more than 10% of hematocrit, or results in signs and/or symptoms of hypovolemia. Uterine atony causes ~ 75% of PPH [3]. PPH is a major cause of maternal mortality, mainly in developing countries, and is the cause of ~ 25% of maternal deaths worldwide [4]. Misoprostol is one of the synthetic PGE1 analogs with strong uterotonic activity and few adverse effects at therapeutic doses [5]. Misoprostol is safe, rapidly absorbed, stable, and easy to be used through oral, vaginal, buccal, or rectal route [6]. Misoprostol has been considered an alternative to injectable uterotonic agents for the prevention of PPH after vaginal or cesarean deliveries [7]. The oral route has the most rapid uptake, but the shortest duration. The rectal route has slow uptake but prolonged duration. The buccal and sublingual routes have rapid uptake, prolonged duration, and greatest total bioavailability [8], with no adverse neonatal effects after the preoperative use of sublingual misoprostol in cesarean delivery [9]. The sublingual route of administration of misoprostol is more effective in reducing intraoperative blood loss [10]. In spite of these numerous amounts of research studies that discuss the role of misoprostol in PPH, there are only few ones that concentrate on the optimum route of administration to prevent the occurrence of PPH and decrease blood loss during cesarean section (CS) on scarred uterus.

The aim of this study was to compare between the effect of preoperative administration of sublingual versus rectal misoprostol on blood loss during and after elective CS when used with 10 IU intravenous oxytocin.


  Patients and methods Top


This randomized controlled clinical trial was conducted in the Obstetrics and Gynecology Department, Faculty of Medicine, Menoufia University Hospital, during the period from September 2019 to July 2020. The aim and steps of the study were explained to the participants, and written informed consent was obtained. The study was approved by the ethical committee of Faculty of Medicine, Menoufia University. The study group was selected regarding the appropriate inclusion and exclusion criteria. Inclusion criteria were uncomplicated singleton pregnancy with gestational age between 37 and 40 weeks (term pregnancy), parity less than 4, and previous CS less than 3. Exclusion criteria were patients with medical disorders (hypertension, diabetes mellitus, severe anemia, and cardiac, pulmonary, chronic endocrine metabolic liver, or kidney disorders), patients with obstetric disorders (polyhydramnios, placenta previa, or any risk factor causing PPH), patients with abnormality detected during sonographic evaluation (e.g. abnormal placenta), and patients with hypersensitivity reaction to misoprostol. Elective cesarean delivery was indicated for patients who had cephalopelvic disproportion, abnormal fetal presentation, or in demand; all CSs were listed and done by the same team, same surgeon, and same technique. All CSs were done under spinal anesthesia. The primary outcome was the amount of intraoperative blood loss. The secondary outcomes were the postoperative blood loss, the change of hematocrit (Hct) level, the incidence of fever, shivering, vomiting, the need for extra-ecbolics, and the need for NICU admission.

Sample size calculation

As intraoperative blood loss was the primary outcome of our study, sample size calculation was performed using G-Power software, version 3.1.9, University of Keil, Germany, to detect a significant difference in intraoperative blood loss. Based on previous studies using the comparison of intraoperative blood loss. Mean ± SD difference in intraoperative blood loss was 99.64 ± 11 (95% confidence interval: 73.81–125.47) to achieve 90% power to detect this difference, with a significance level of 5%. The minimal calculated sample size was 45 women in each group, with a total of 135 in all groups would be needed to detect this difference at a similar or narrower confidence interval. The 135 participants were randomized into three equal groups (rectal, sublingual, and control) using a computer-generated list (MedCalc Software, version 19.0.2; Acacialaan 22, Ostend, Belgium), as shown in CONSORT flow chart [Figure 1]. Group allocation was concealed in sealed opaque envelops kept with a health care provider. Each participant received the corresponding drug administration according to her order of participation in this trial by the health care provider who was not participating in the study. Full history, general examination, obstetric examination, routine investigation, and obstetrics ultrasound were done for all participants. The amniotic fluid index (AFI) was estimated and amniotic fluid volume (ml) was calculated by multiplying AFI (cm) by 30. Hemoglobin (Hb) level and Hct were measured before CS and 24 h after CS. CS was performed under spinal anesthesia, the patient was catheterized, and then the rectal or sublingual tablets were administered according to the randomization plan. Group I (rectal) received 400 μg misoprostol rectally, group II (sublingual) received 400 μg misoprostol sublingually, group III (control) did not receive misoprostol. All cases received 10 IU of oxytocin by slow intravenous injection after cord clamping. The linen towels were weighed (g) with its wrapping before and after the operation using a highly accurate digital balance. Blood loss during the operation was calculated using the following factors: volume of the contents of the suction bottle (ml) (A), difference in weight of linen towels (g) (B) [weight of soaked linen towels (g)−weight of dry linen towels (g)], and amniotic fluid volume (ml) (C), so blood loss during operation (ml)=(A + B)–C [11]. Postoperative blood loss during 24 h was calculated as follows: difference in weight of diapers in g (D)=[weight of wet diapers (g)–weight of dry diapers (g)], so total blood loss during and after operation =(A+B) - C + (D). Adverse effects such as fever, hyperpyrexia, shivering, vomiting, and need for ICU were recorded. Additional uterotonics therapy was also recorded, and the neonatal outcome (NICU admission) was reported.
Figure 1: Study CONSORT chart.

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Statistical analysis

It was done using statistical package for social sciences (SPSS 22.0 for Windows, SPSS Inc., Chicago, Illinois, USA). The results were represented as mean ± SD for quantitative data and by number (%) for qualitative data. Comparisons between the groups were conducted by Student t test for parametric data and by Mann–Whitney test for nonparametric data. χ2 test was used to test the significance between groups regarding qualitative data. P value was assumed significant if less than 0.05 and highly significant if P value was less than 0.001.


  Results Top


A CONSORT flow chart of the study population is shown in [Figure 1]. Of the 150 women enrolled (15 participants were excluded, and 135 women included), 45 women were allocated to each group. Our results demonstrated that there were no significant differences between the studied groups regarding age, BMI, parity, gestational age, number of previous cesarean delivery, preoperative Hb, preoperative Hct, and AFI (P > 0.05) [Table 1]. Our results demonstrated that there were statistically significantly differences between the studied groups regarding intraoperative blood loss (PI/II = 0.007 vs. PI/III < 0.001 and PII/III ≤ 0.001) and postoperative estimated blood loss (PI/II = 0.006 vs. PI/III < 0.001 and PII/III < 0.001). It was higher in group III and lowest in group II [Table 2]. The results demonstrated that there were statistically significant differences between misoprostol groups and control group, whereas no significant difference was shown between rectal and sublingual groups regarding postoperative Hb (PI/II = 0.256 vs. PI/III = 0.002 and PII/III < 0.001) and postoperative Hct (PI/II = 0.32 vs. PI/III = 0.009 and PII/III < 0.001) [Table 3]. There were no statistically significant differences among the studied groups regarding fever, shivering, vomiting, NICU, and need for extra-ecbolics (P > 0.05) [Table 4].
Table 1: Comparison between study groups regarding demographic characteristics, preoperative hemoglobin, preoperative hematocrit, and amniotic fluid index

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Table 2: Comparison among study groups regarding intraoperative estimated blood loss and postoperative estimated blood loss (ml)

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Table 3: Comparison between study groups regarding postoperative hemoglobin, change in hemoglobin (Δhemoglobin), postoperative hematocrit, and change in hematocrit (Δhematocrit)

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Table 4: Comparison among the study groups regarding the incidence of adverse effects

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  Discussion Top


Statistically significant differences were found among all groups regarding intraoperative blood loss. It was highest in group III (control), then group I (rectal), and lowest in group II (sublingual). This agreed with the study done by Sweed et al. [12], in which the mean intraoperative blood loss was 641.7 ± 135.7 ml in nonmisoprostol group and was lower in both misoprostol groups: rectal group and sublingual group were 457.5 ± 140.7 and 357.8 ± 129.7 ml, respectively. Another study done by Ibrahim[10] agreed with our results. They showed that women of rectal misoprostol group had a significantly higher amount of intraoperative blood loss (581 ± 96 ml) compared with sublingual misoprostol group. Moreover, our results were in agreement with a study done by Omozuwa and Okonkwo [5]. They found mean intraoperative blood loss was significantly less in the sublingual group compared with the rectal group (602.87 ± 131.96 vs. 705.83 ± 142.24 ml, respectively). There were statically significant differences among all groups regarding the difference in postoperative blood loss. It was highest in group III (control), then group I (rectal) and lowest in group II (sublingual). This agreed with a study done by Elsedeek [13], which found the mean postoperative blood loss was significantly lower in the study group than the control group (185 ± 95 vs. 324 ± 167 ml, respectively). The difference between the rectal and sublingual groups may be related to the rapid absorption, and high bioavailability of misoprostol when given sublingually. On the contrary, a study done by Bhullar et al.[14] found no difference when using 200 μg of misoprostol in comparison with placebo, which is owing to the uncertainty of the lowest effective dose of misoprostol. In our study, regarding the postoperative Hb and Hct, no significant reduction was found in postoperative Hb and Hct in misoprostol groups (group I and group II), whereas there was a significant reduction found in the control group. Moreover, the percentage of Hct reduction was elevated in the rectal group compared with the sublingual group. These results agreed with the study done by Sweed et al. [12]. They found postoperative Hb and Hct were decreased to 10.3 ± 1.0 and 33.3 ± 2.4 in sublingual group, 10.1 ± 1.0 and 33.4 ± 3.0% in rectal group, and 9.7 ± 1.1 and 31.8 ± 2.7% in control group, respectively. There was no significant difference between both sublingual and rectal misoprostol groups. These results also agreed with the study done by Ibrahim [10], who found the postoperative Hb and Hct were decreased to 10.28 ± 0.88, 32.1 ± 2.1% and 10.14 ± 0.67, 31.5 ± 2.7% in both sublingual and rectal misoprostol groups, respectively. In agreement with our result, another study done by Nayak et al.[15] reported that sublingual misoprostol group showed significant decrease in total blood loss (around 117.9 ml) as compared with the control group. Sublingual misoprostol group also showed decrease in postoperative fall in hematocrit as compared with control. Our study results agreed also with a study done by Sitaula et al. [16]. They concluded that preoperative rectal misoprostol was found to be an effective measure to reduce the intraoperative and postoperative blood loss during elective cesarean delivery. In the present study, there was no statistically significant difference among all groups concerning the need of additional uterotonics. This result coincides with a study done by Sweed et al. [12], which found no significant difference regarding this outcome. Regarding the need for blood transfusion, in this study, there was no need for any blood transfusion among all the groups. This result coincides with a study done by Ibrahim [10]. On the contrary, this result disagrees with a study done by Sweed et al.[12] who found a significant need for blood transfusion in all groups. We presume that this need for blood transfusion was owing to their study inclusion criteria, which included anemic cases (Hb ≥ 8). Regarding the need of neonatal ICU, this study found no significant difference among the three groups. This result indicates safety of administering 400 μg. misoprostol while the fetus was still in utero. This result coincides with a study done by Sweed et al. [12]. Regarding adverse effects of misoprostol, fever, shivering, and vomiting, there were no significant statistical differences among all study groups. These results are in agreement with the study done of Ibrahim[10] (except for vomiting which was higher in sublingual misoprostol group). Shivering, pyrexia, and vomiting are notable adverse effects associated with the use of misoprostol. Shivering compared with pyrexia and vomiting was significantly noted with the sublingual group. This can be explained by the fact that sublingual route tends to have better systemic absorption than the rectal route [4]. These adverse effects however were noted to be transient and dose dependent.

The following were the strength points in our study: it was randomized controlled clinical trial study, conducted on three groups including control group, targeted scarred uterus cases, and the study outcomes were compared with very recent studies. Study limitations were the relatively small sample size, it is a single-center study, concentrated on low-risk group for PPH, and some of the study outcomes are dependent on the reliability of laboratory results.


  Conclusion Top


Misoprostol with oxytocin is an effective drug combination to prevent PPH and decrease intraoperative blood loss during CS with better results through sublingual than rectal route.

Financial support and sponsorship

Nil.

Conflicts of interest

Ther are no conflicts of interest.



 
  References Top

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Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR. The increasing trend in caesarean section rates: global, regional and national estimates. PLoS One 2016; 11:0148343.  Back to cited text no. 1
    
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World Health Organization. WHO statement on caesarean section rates. Geneva: World Health Organization; 2015.  Back to cited text no. 2
    
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Fukami T, Koga H, Goto M, Ando M, Matsuoka S, Tohyama A, et al. Incidence and risk factors for postpartum hemorrhage among transvaginal deliveries at a tertiary perinatal medical facility in Japan. PLoS One 2019; 14:0208873.  Back to cited text no. 3
    
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Nankaly A, Jalilian N, Eshghiali SO, Rezaei M. The effects of sublingual misoprostol and intravenous oxytocin in reducing bleeding among cesarean deliveries. Acta Med Mediter 2016; 32:953–957.  Back to cited text no. 4
    
5.
Omozuwa ES, Okonkwo CA. Randomized controlled trial of sublingual and rectal misoprostol administration on blood loss at elective caesarean section. Eur J Biol Med Sci Res 2018; 7:1–18.  Back to cited text no. 5
    
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Rajaei M, Karimi S, Shahboodaghi Z, Mahboobi H, Khorgoei T, Rajaei F. Safety and efficacy of misoprostol versus oxytocin for the prevention of postpartum hemorrhage. J Pregnancy 2014; 20:23–32.  Back to cited text no. 6
    
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Conde-Agudelo A, Nieto A, Rosas-Bermudez A, Romero R. Misoprostol to reduce intraoperative and postoperative hemorrhage during cesarean delivery: a systematic review and meta-analysis. Am J Obstet Gynecol 2013; 209:40–41.  Back to cited text no. 7
    
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Hofmeyr GJ, Walraven G, Gülmezoglu AM, Maholwana B, Alfirevic Z, Villar J. Misoprostol to treat postpartum haemorrhage: a systematic review. BJOG 2005; 112:547–553.  Back to cited text no. 8
    
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Ayati S, Vahidroodsari F, Farshidi F, Shahabian M, Aghaee MA. Vaginal versus sublingual misoprostol for labor induction at term and post term: a randomized prospective study. Iran J Pharma Res 2014; 13:299.  Back to cited text no. 9
    
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Ibrahim MM. Comparison between the effect of sublingual and rectal misoprostol on hemoglobin level change before and after caesarean section. Egypt J Med Res 2020; 1:13–23.  Back to cited text no. 10
    
11.
Lapaire O, Schneider MC, Stotz M, Surbek DV, Holzgreve W, Hoesli IM Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery. Int J Gynaecol Obstet 2006; 95:2–7.  Back to cited text no. 11
    
12.
Sweed MS, El-Saied MM, Abou-Gamrah AE, El-Sabaa HA, Abdel-Hamid MM, Hemeda H, et al. Rectal vs. sublingual misoprostol before cesarean section: double-blind, three-arm, randomized clinical trial. Arch Gynecol Obstet 2018; 298:1115–1122.  Back to cited text no. 12
    
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Elsedeek MS. Impact of preoperative rectal misoprostol on blood loss during and after elective cesarean delivery. Int J Gynecol Obstet 2012; 118:149–152.  Back to cited text no. 13
    
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Bhullar A, Carlan SJ, Hamm J, Lamberty N, White L, Richichi K. Buccal misoprostol to decrease blood loss after vaginal delivery: a randomized trial. Obstet Gynecol 2004; 104:1282–1288.  Back to cited text no. 14
    
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Nayak L, Pradhan K, Mishra S. Role of 400 mcg intraoperative sublingual misoprostol for reduction of caesarean blood loss. J Evid Based Med Healthcare 2017; 4:573–577.  Back to cited text no. 15
    
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Sitaula S, Uprety DK, Thakur A, Pradhan T. Impact of preoperative rectal misoprostol on blood loss during and after elective cesarean delivery: a randomized controlled trial. Nepal J Obstetr Gynaecol 2017; 11:37–41.  Back to cited text no. 16
    


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