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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 4  |  Page : 1333-1337

Comparison of the effect of carbetocin versus oxytocin during cesarean section in women with high risk of postpartum hemorrhage


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

Date of Submission24-Apr-2018
Date of Decision28-May-2018
Date of Acceptance01-Jun-2018
Date of Web Publication31-Dec-2019

Correspondence Address:
Abeer A A Emara
Shebin El-Kom, Menoufia 57512
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_160_18

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  Abstract 


Objectives
To compare the hemodynamic effects of oxytocin and carbetocin and to assess the efficacy of these two drugs in terms of blood loss and the additional uterotonic needed in cesarean section in women with high risk of primary postpartum hemorrhage (PPH).
Background
Prevention of PPH is a major issue owing to its effect on maternal morbidity and mortality. Although oxytocin is the most widely accepted uterotonic agent, carbetocin can be given as an intravenous bolus instead of continuous oxytocin infusion.
Patients and methods
This is a prospective, randomized controlled study conducted from March 2016 and October 2017 within the Department of Obstetrics and Gynecology in Menoufia University Hospitals. The study included 100 pregnant women with high risk of PPH; women were divided randomly into group A, which received oxytocin infusion of 20 international units, and group B, which received 100 μg carbetocin as an intravenous bolus.
Results
Regarding the hemodynamic effects, there was a significant lower reduction in blood pressure within the oxytocin group. Significantly more women needed additional uterotonic agents in the oxytocin group. Uterine fundal level was significantly below 2 cm from the umbilical point in carbetocin group. The mean cost in oxytocin group is lower with a highly significant difference.
Conclusion
Single injection of carbetocin has more safe hemodynamic profile and less need of uterotonics, but the introduction of oxytocin appears to provide improved clinical outcomes along with cost savings.

Keywords: carbetocin, oxytocin, postpartum hemorrhage, uterotonic drugs


How to cite this article:
Abdelhamid AN, Sayyed TM, Hamza HA, Emara AA. Comparison of the effect of carbetocin versus oxytocin during cesarean section in women with high risk of postpartum hemorrhage. Menoufia Med J 2019;32:1333-7

How to cite this URL:
Abdelhamid AN, Sayyed TM, Hamza HA, Emara AA. Comparison of the effect of carbetocin versus oxytocin during cesarean section in women with high risk of postpartum hemorrhage. Menoufia Med J [serial online] 2019 [cited 2020 Jan 20];32:1333-7. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1333/274220




  Introduction Top


Prevention of postpartum hemorrhage (PPH) is a major issue owing to its effect on maternal morbidity and mortality. The primary PPH is defined as blood loss more than 500 ml after vaginal delivery and more than 1000 ml after cesarean section that occurs in the first 24 h after delivery [1]. The first cause of hemorrhage at the time of delivery is uterine atony; therefore, there is general agreement that active management of the third stage of labor rather than expectant management should be initiated [2]. The administration of uterotonic drugs widely prevents the PPH; therefore, it is the main point of active management. Among uterotonics, oxytocin has proven to be very effective in reducing the incidence of PPH [3]. Although oxytocin is the most widely accepted uterotonic agent, a lot of data from the literature suggest that prophylactic administration of carbetocin may be a good alternative to oxytocin to prevent PPH; however, which uterotonic agent is ideal for prophylactic use is being debated [4]. The aim of this study was to compare both drugs regarding effectiveness, safety, and hemodynamic effects during cesarean sections in women with high risk of PPH.


  Patients and Methods Top


This is a prospective, single-center, randomized controlled study conducted from March 2016 to October 2017 within the Department of Obstetrics and Gynecology in Menoufia University Hospitals. The local ethical committee at Menoufia University Hospital approved the study protocol, and an informed consent was obtained from all participants before commencing the study. The study was conducted on 100 pregnant women with high risk of PPH, who underwent elective or emergency cesarean section under spinal anesthesia. The study included pregnant women with risk factors for primary PPH such as multiple pregnancies, previous cesarean scar, presence of uterine fibroids, previous myomectomy, presence of placenta previa, past history of PPH, fetal macrosomia, and fetal polyhydramnios. Exclusion criteria were the presence of hypertension, preeclampsia, cardiac diseases, renal diseases, liver diseases, epilepsy, general anesthesia, and women with history of hypersensitivity to carbetocin. On the basis of selection criteria, 100 pregnant women were divided randomly into two groups according to a random allocation sequence developed via a random number table in a statistical textbook and was distributed through sequenced opaque closed envelopes, where each envelope contained a single assignment.

All participants were subjected to detailed history, with special reference to patient demographics, including age and weight, present history and information on the current pregnancy. Menstrual history, obstetric history, medical history, comorbidities, and comedications were collected. A standardized protocol for anesthesia was followed for all patients. After the application of the spinal anesthesia, the women were positioned in a left-tilted recumbent position. For blood pressure measurement, a limb cuff was applied. Laparotomy was performed by Pfannenstiel incision. Followed by uterine incision, delivery of the baby, cord clamping then finally the placenta was delivered through cord traction. For uterine repair, the uterus was exteriorized. After delivery of the fetus, the study drug was administered by the anesthetist. Women in the group A received 20 IU of oxytocin (Syntocinon; Hameln Pharmaceuticals Ltd. Nexus, Gloucester Business Park Gloucester, GL3 4AG, United Kingdom) in 1000 ml of 0.9% NaCl solution intravenous (150 ml/h), and women in the group B received 100 μg intravenous carbetocin (PABAL; Ferring Pharmaceuticals Ltd, Drayton Hall Cottages, Church Rd, West Drayton UB77PS, United Kingdom) bolus over 1 min. Baseline blood pressure (systolic and diastolic) was recorded before skin incision, and then recorded at skin incision; 1, 3, and 5 min after drug administration; at time of uterine repair; suturing the skin; and 2, 12, and 24 h after cesarean section. The need for additional uterotonic medication after carbetocin or oxytocin administration was recorded. Occurrence of nausea, vomiting, flushing, and tachycardia (increase 20% of baseline pulse) was recorded. Blood loss during the operation was estimated through volume of blood in a graduated suction jar and the change in weight of sponges soaked with blood; moreover, the amount of bleeding vaginally was also noted during first 2 h after operation by the change in weight of sponges. Uterine tone was assessed based on a 10-point linear analog scale (0 = floppy and 10 = maximum contraction) through palpation intraoperative at 3, 6, 9 and 12 min after uterotonic injection. Evaluation of the drop in hemoglobin level by comparing the hemoglobin concentration on admission with the measure at 2 and 24 h after delivery.

Uterine position (with respect to the umbilical point) was monitored 2 and12 h after delivery. All patients had the Foley catheter and urobag in situ, and the amount of urine was monitored 2 and 12 h after delivery.

Statistical analysis

Data were collected, tabulated, and statistically analyzed by a computer using SPSS (version 16; SPSS Inc., Chicago, Illinois, USA). The mean (X̄) and SD were used as descriptive statistics. Student's t test was used for comparison between two means of normal distributed data. Checking the normality of data was done by Kolmogorov–Smirnov test. P value less than 0.05 was set to be significant.


  Results Top


The current study included 100 women undergoing cesarean section with high risk of PPH. Oxytocin group (group A) included 48 women, and carbetocin group (group B) included 52 women. Systolic blood pressure was significantly lower in the oxytocin group at the third and fifth minute after administration, at the time of uterine closure, and 12 and 24 h postoperatively (P = 0.01, 0.04, 0.01, 0.011, and 0.011, respectively) [Table 1]. However, diastolic blood pressures were pairwise lower in the oxytocin group at the third and fifth minutes after administration, and 12 and 24 h postoperatively; this reduction in diastolic blood pressure was statically significant (P = 0.02, 0.018, 0.003, and 0.003, respectively) [Table 2]. We find that 7.7% of the patients from the carbetocin group versus 27.1% from the oxytocin group needed additional uterotonic agents. Therefore, there is a highly significant need of additional uterotonic agents in the oxytocin group (P < 0.001) [Figure 1]. There was no statistically significant difference between both drugs regarding uterine contractility [Figure 2]. The fundus was significantly below 2 cm from the umbilical point (−2 UP) in patients of carbetocin group at 2 and 12 h in the ward in comparison with patients undergoing oxytocin administration [Figure 3]. The mean cost of oxytocin group was 27.4 ± 5.1 Egyptian pounds whereas in carbetocin group, it was 110.9 ± 3.2 Egyptian pounds. There was a highly statistically significant difference between both groups regarding the cost (P < 0.001) [Table 3].
Table 1: Systolic blood pressure (mm Hg) during and after cesarean section

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Table 2: Diastolic blood pressure (mm Hg) during and after cesarean section

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Figure 1: The need of additional uterotonic drug.

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Figure 2: Uterine tone in both groups in relation to time.

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Figure 3: Uterine position in relation to the umbilical point.

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Table 3: Cost of both drugs

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  Discussion Top


To the best of our knowledge, this is one of the few studies that compared carbetocin with oxytocin in cesarean sections among women with risk factors for PPH. Nonetheless, up to date, which uterotonic agent is suitable for prophylactic use is still being debated, and the literature lacks clear end points on this issue. The primary outcome of our study was to assess the efficacy of oxytocin and carbetocin in terms of intraoperative blood loss, the additional uterotonic needed, and the hemodynamic effects of both drugs in cesarean sections in women with high risk of PPH. Our results have shown that when compared with oxytocin, carbetocin was comparable in efficacy with oxytocin in prophylaxis and prevention of PPH, and there were no cases complicated with PPH in both groups. Moreover, the number of participants with blood loss range (500–1000 ml) in carbetocin group did not differ statistically from their counterparts in oxytocin group. In agreement, Attilakos et al. [4] have found no significant difference in the amount of bleeding between oxytocin and carbetocin groups. We found a definitively lack of additional uterotonic need after cesarean section in the carbetocin receiving women at high risk for PPH. Regarding the literature about carbetocin, Dansereau et al. [5] first described a lower additional uterotonic need for treatment of uterine atony in women who took carbetocin soon after delivery. Moreover, Borruto et al. [6] described a lower rate of additional uterotonic need in women undergoing carbetocin administration during cesarean section. Our results agreed with those of Samimi et al. [7] who randomized 200 women undergoing vaginal delivery to receive either carbetocin or syntometrine to prevent PPH. They found that the need for additional uterotonics was significantly lower in carbetocin group. They concluded that carbetocin is more effective than syntometrine in the prevention of PPH. Our results are also in agreement with those of Maged et al. [8] who randomized 100 women delivering vaginally with at least two risk factors of atonic PPH to receive 100 μg intravenous of carbetocin or 5 IU intramuscular of oxytocin. They found that the amount of bleeding, occurrence of PPH, and need for other uterotonics were significantly lower in carbetocin group. Attilakos et al. [4] randomized 377 women undergoing cesarean sections to receive either intravenous carbetocin 100 μg or intravenous oxytocin 5 IU after the delivery of the baby. The carbetocin group needed significantly less uterotonic drugs, which agrees with our findings. Considering the hemodynamic effects of both drugs, it was shown that oxytocin participant group had more hypotension than carbetocin group, with a statistical significant difference. In agreement, we report a good hemodynamic profile in carbetocin group with substantially unmodified levels of systolic and diastolic blood pressures with respect to the beginning of the surgical procedure; moreover, we found lower blood pressure levels among the oxytocin group in almost all the study group after drug administration. This result suggests that carbetocin seems to have an acceptable hemodynamic safety profile. A study of Moertl et al. [9] concluded that patients treated with oxytocin have a more pronounced hypotension and hemodynamic rebound than patients treated with carbetocin, with comparable effects on the cardiovascular system. These hemodynamic adverse effects of oxytocin, especially in patients with hypervolemia or cardiac diseases, may lead to myocardial ischemia [10]. On this item, Su et al. [11],[12] in the Cochrane of 2007 regarding 'Oxytocin agonists for preventing postpartum hemorrhage' and in the Cochrane 2012 regarding 'Carbetocin for preventing postpartum hemorrhage,' concluded that the use of carbetocin is more effective than oxytocin for preventing PPH in women undergoing cesarean section, but the data and the evidences were still insufficient. We did not demonstrate any difference in the drop of hemoglobin level within 2 and 24 h. Samimi et al. [7] and Maged et al. [13] have found that the mean fall of hemoglobin before and after delivery was lower in the carbetocin group, but our results have not shown this difference. Larciprete et al. [14] suggested the effectiveness of carbetocin compared with oxytocin regarding the uterine contraction and tonicity. They have shown that the uterine contractility was better in the carbetocin group at 2, 12, and 24 h after cesarean section, as well as the fundus was significantly below 2 cm from the umbilical point (−2 UP) in patients receiving carbetocin after 2 and 12 h. This can be explained by the known longer half-life of carbetocin effecting more uterine response, in terms of frequency and amplitude of uterine contractions [15].

However, we found that the uterine contractility was similar in both groups and that the fundus was significantly below 2 cm from the umbilical point (−2 UP) in patients of carbetocin group at 2 and 12 h. In our study, there was no significant difference between both groups regarding the occurrence of nausea, vomiting, tachycardia, and flushing. These results agreed with those of Maged et al. [13], Moertl et al. [9], and Attilakos et al. [4] who found no significant difference in the adverse effects between carbetocin and oxytocin. Regarding the effects of both drugs on the urine output, we observed no significant difference in diuresis. This result is against those of Larciprete et al. [14] who found a significant difference in the diuresis, being higher in carbetocin group. Finally, in our study, we found that the use of oxytocin for prevention of PPH at cesarean section was associated with cost saving of ∼82.5 Egyptian pounds compared with the use of carbetocin for prevention of PPH at cesarean section. This is against the study of van der Nelson et al. [16] which was done in the UK, which found that the use of carbetocin compared with oxytocin for prevention of PPH at cesarean section was associated with a cost saving of ≤27 518. This can be explained by the more expensive drug list and less availability of drugs in our country.

Limitation of this work

The subjective assessment of the uterine tone and the small sample size were the main limitations.


  Conclusion Top


We concluded that carbetocin is an effective drug as the oxytocin for prevention and prophylaxis of PPH and a single injection of carbetocin appears to have a safer hemodynamic profile and less need for uterotonics. However, the introduction of oxytocin appears to provide improved clinical outcomes along with cost savings; it is an inexpensive medicine and is easily available.

Acknowledgements

The authors acknowledge the contribution of the residents and the nursing staff of the operation room of Menoufia University Hospital.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
Knight MM, William MC, Cynthia B, Sophie A, Marie HB, Jane BF. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy and Childbirth 2009; 46:508–514.  Back to cited text no. 2
    
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Rozenberg P, Quibel T, Ghout I, Salomon L, Bussiere L, Goffinet F. Active management of the third stage of labor with routine oxytocin and misoprostol for the prevention of postpartum hemorrhage: a randomized controlled trial. Am J Obstet Gynecol 2016; 212 (Suppl. 1):S18.  Back to cited text no. 3
    
4.
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Dansereau J, Joshi AK, Helewa ME, Doran TA, Lange IR, Luther ER. Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section. Am J Obstet Gynecol 1999; 180:670–676.  Back to cited text no. 5
    
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Samimi MIA, Abedzadeh-Kalahroudi M. Carbetocin vs. syntometrine in prevention of postpartum hemorrhage: a double blind randomized control trial. Iran Red Crescent Med J 2013; 15:817–822.  Back to cited text no. 7
    
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Maged AM, Hassan AMA, Shehata NAA. Carbetocin versus oxytocin in the management of atonic post partum haemorrhage (PPH) after vaginal delivery: a randomised controlled trial. Arch Gynecol Obstet 2016; 293:993–999.  Back to cited text no. 8
    
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Moertl MG, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach D. Haemodynamic effects of carbetocin and oxytocin given as intravenous bolus on women undergoing caesarean delivery: a randomised trial. BJOG 2011; 118:1349–1356.  Back to cited text no. 9
    
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Larciprete G, Carlotta M, Mariagrazia F, Valentina P, Cristina T, Benedetta Z. Carbetocin versus oxytocin in caesarean section with high risk of post-partum haemorrhage. J Prenatal Med 2013; 7:12–18.  Back to cited text no. 14
    
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