|Year : 2018 | Volume
| Issue : 5 | Page : 279-283
Ten units intravenous oxytocin over 2–4 h is as effective as 30 units over 8–12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial
Maria Cecilia, Reeta Vijayaselvi, Ramandeep Bansal, Latha Lakshmi, Ruby Jose
Department of Obstetrics and Gynecology, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||29-Aug-2018|
|Date of Acceptance||26-Oct-2018|
|Date of Web Publication||14-Dec-2018|
Dr. Ramandeep Bansal
Advanced Skin and Medicine Clinic, Sector 44 A, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
OBJECTIVES: Currently, recommended high-dose oxytocin regimen for the prevention of postpartum hemorrhage (PPH) following cesarean delivery (CD) is associated with maternal side effects frequency of which is greater with a higher cumulative dose and rapid administration of oxytocin. Here, we evaluated the efficacy of single-dose intravenous oxytocin over 2–4 h (total = 10 units) with oxytocin maintenance infusion for 8–12 h (total = 30 units) in postoperative CD women for the prevention of PPH.
METHODS: The current double-blinded randomized controlled trial was carried out in a tertiary care institute in Southern India. The primary outcome measures included the following: (a) the need for additional uterotonics to control PPH and (b) significant deterioration of vital signs as assessed by pulse rate and blood pressure in the postoperative period. The secondary outcome measures were as follows: (a) significant difference (≥10% between preoperative and postoperative packed cell volume) and (b) need for blood transfusion.
RESULTS AND CONCLUSIONS: Two hundred and seventy-one women were randomized into Group A (oxytocin = 10 units; n = 135) and Group B (oxytocin = 30 units; n = 136). Both the groups were comparable with regard to demographic characteristics. There was no difference in any of primary or secondary outcome measures in the two groups. Thus, low-dose oxytocin regimen is as effective as high-dose oxytocin regimen in the prevention of PPH in postoperative CD women.
Keywords: Cesarean delivery, oxytocin, postpartum hemorrhage
|How to cite this article:|
Cecilia M, Vijayaselvi R, Bansal R, Lakshmi L, Jose R. Ten units intravenous oxytocin over 2–4 h is as effective as 30 units over 8–12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial. Indian J Pharmacol 2018;50:279-83
|How to cite this URL:|
Cecilia M, Vijayaselvi R, Bansal R, Lakshmi L, Jose R. Ten units intravenous oxytocin over 2–4 h is as effective as 30 units over 8–12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial. Indian J Pharmacol [serial online] 2018 [cited 2019 Mar 24];50:279-83. Available from: http://www.ijp-online.com/text.asp?2018/50/5/279/247535
| » Introduction|| |
Postpartum hemorrhage (PPH) is a major cause of maternal mortality accounting for 25% of all pregnancy-related deaths. The incidence of PPH is higher after cesarean delivery (CD). Furthermore, average blood loss after a CD is higher (1000 ml) than after a vaginal delivery (500 ml) and approximately 6% of women experience excessive blood loss as indicated by 10% or more drop in hematocrit after CD.,,, Thus, the importance of measures to reduce the incidence and severity of PPH after CD cannot be overemphasized.
Oxytocin, a pituitary hormone, is used routinely to reduce the incidence and severity of PPH following normal delivery as well as CD. However, its use is complicated by several maternal side effects, the frequency of which is greater with a higher cumulative dose and rapid administration of oxytocin. To overcome these side effects, several low-dose oxytocin regimens have been developed in the last decade for the prevention of PPH following CD. However, most of the data regarding the efficacy of low-dose regimens are from the Western world, and the results may not be applicable to developing countries where the etiological factors responsible for PPH are different. Furthermore, the consequences of PPH are likely to be worse in developing world due to the high prevalence of anemia and malnutrition.
In our institute, it has been a routine practice to give 10 units of oxytocin infusion over 2–4 h after delivery of the baby during CD. Postoperatively, two more pints of intravenous (IV) fluids each with 10 units of oxytocin are given over 8–12 h. Based on current recommendations, wherein lower dosage of oxytocin is also found to be effective in the prevention of PPH after CD; we planned this study to evaluate the efficacy of a lower dose regimen compared to high-dose regimen in the prevention of PPH following CD.
Aims and objectives
To compare single-dose IV oxytocin over 2–4 h (total = 10 units) with oxytocin maintenance infusion for 8–12 h (total = 30 units) in postoperative CD women to prevent PPH.
| » Methods|| |
The current double-blinded randomized controlled trial was carried out in the Department of Obstetrics and Gynecology at a tertiary care institute and referral center in Southern India, for 1 year commencing from October 2011. Informed consent was obtained from all the patients before enrollment, and ethical clearance was obtained from the Institutional Ethics Committee before the commencement of the study. Randomization was done using computer-generated allocation numbers. For allocation concealment, these numbers were kept in sealed covers and were opened only after CD. The investigator, the person involved in caring of postoperative patients, and the statistical analyzer were blinded. All the women, who underwent elective and emergency CD during the study period, were included in the study if they gave informed consent. The exclusion criteria included the following: (a) anemia (Hemoglobin <8 g/dl); (b) placenta previa; (c) abruptio placenta; (d) hemolysis, elevated liver enzymes, and low platelet syndrome; (e) presence of bleeding disorders; (f) intraoperative atonicity of uterus requiring additional uterotonics or severe intraoperative blood loss requiring blood transfusion: (g) severe fetal distress (when there is no time to counsel patients); and (h) previous h/o PPH. Once randomized the women in Group A were given 10 units of oxytocin intravenously in 500 ml of IV fluids over 2–4 h while women in Group B were given 30 units of oxytocin intravenously in 1500 ml IV fluids over 8–12 h. All the participants were followed carefully according to the protocols being followed in our institute. All the women were reviewed by an intern medical officer and a postgraduate medical student with full experience in emergency obstetric care. All the women were monitored extensively for the first 4 h with hourly monitoring of vital signs and blood loss. After this, they were monitored every 2–4 h. All the outcome measures as well as other details were noted on a predesigned pro forma.
The primary outcome measures included the following: (a) the need for additional uterotonics to control PPH and (b) significant deterioration of vital signs as assessed by pulse rate and blood pressure (BP) in the postoperative period. The secondary outcome measures were as follows: (a) significant difference (≥10% between preoperative and postoperative packed cell volume [PCV]) and (b) need for blood transfusion.
All the data were entered into SPSS version 20 (IBIBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). Mean, median, and range were used to describe the distribution of data. The Chi-square test was used to compare the variables qualitatively while the Student's t-test was used for the quantitative analysis of different variables. P < 0.05 was taken as statistically significant.
| » Results|| |
The current study included 271 women. There were 135 patients in Group A (oxytocin = 10 units) and 136 in Group B (oxytocin = 30 units). The mean age of the women in Group A was 26.9 ± 6.4 years, and in Group B, it was 27.6 ± 6.2 years. In Group A, 55 (40.7%) women were primigravida, while in Group B, 51 (37.5%) women were primigravida. The mean gestational age was 270 days in both the groups. The main medical problems seen in Group A were as follows: hypertension (10%–8.8%), diabetes mellitus (11%–8.1%), and previous CS (54%–40%). The corresponding frequency of these disorders in Group B was as follows: hypertension (10%–7.4%), diabetes mellitus (9%–6.6%), and previous CD (57%–41.9%).
While in Group A, labor was spontaneous in 19 (14.1%) and induced and/or augmented in 40 (29.2%) women, respectively, the corresponding figures for Group B were 21 (15.4%) and 34 (25%) women, respectively. The mean induction to delivery interval and augmentation to delivery times were 1140 min and 720 min, respectively, in Group A and 1140 min and 480 min, respectively, in Group B. The preterm premature rupture of membranes and premature rupture of membranes was seen in 3 (2.2%) and 13 (9.6%) women in Group A and in 2 (1.5%) and 6 (4.4%) women in Group B, respectively. Amnioinfusion was given in 3 (2.2%) women in Group A and 1 (0.7%) woman in Group B. Type of CD was elective in 19 (14.1%) women and emergency in 116 (85.9%) women in Group A while corresponding figures for Group B were 29 (21.3%) and 107 (78.7%), respectively. The most common indications for CD in Group A were fetal distress (111%–82.2%) and failed induction 7 (5.2%). Similarly, the most common indications for CS in Group B were fetal distress (122%–89.7%) and failed induction (9%–6.6%). The preoperative PCV was 34.4 in Group A and 36.6 in Group B. The duration of CS was 31.3 min in Group A and 33.3 min in Group B. The mean weight of the baby was 2847 g in Group A and 2896 g in Group B. These parameters were comparable in both the groups as shown in [Table 1].
Among the primary outcome measures, one woman each in both groups required the administration of additional uterotonics. Similarly, only one woman in each group developed PPH. The mean numbers of mops used were 6.5 in Group A and 6 in Group B (P = 0.63). The number of fully soaked mops was 3.5 in Group A and 4 in Group B (P = 0.42). The total mean estimated blood loss was 400 ml in both the groups (P = 0.44). In Group A, atonic uterus was seen in 1 (0.7%), and in Group B, it was seen in 7 (5.1%) women (P = 0.03). Postoperative fall in BP or tachycardia was seen in 10 women in Group A and in 12 women in Group B (P = 0.87). The mean postoperative PCV was 34.06 patients in Group A and 34.5 in Group B (P = 0.56). The mean fall in PCV was also comparable in both the groups. Blood transfusion in the ward was needed in 6 (4.4%) patients in Group A and 7 (5.1%) patients in Group B (P = 0.92). Chest pain as complained by 10 women in Group B and none in Group A.
Thus, all the outcome measures were comparable in both groups. These results can be seen in [Table 2].
|Table 2: Comparison of primary and secondary outcome measures in both the groups|
Click here to view
| » Discussion|| |
Routine prophylactic use of oxytocin reduces the incidence of PPH by approximately 40% resulting in decrease in maternal morbidity and morbidity.,, However, there is still no consensus regarding dose and rapidity of administration of oxytocin. While high doses of oxytocin may be more effective in preventing uterine atony following CD, these are associated with significant side effects such as hypotension, nausea, vomiting, chest pain, headache, flushing, myocardial ischemia, ST-T segment changes, pulmonary edema, and severe water intoxication with convulsions.,,, Thus, there is an urgent need for treatment protocols based on lower doses of oxytocin, which are associated with fewer maternal adverse effects without compromising on efficacy in the prevention of PPH.
In the current study, we compared one such protocol using single-dose IV oxytocin over 2–4 h (total = 10 units) with oxytocin maintenance infusion for 8–12 h (total = 30 units) in postoperative CD women to prevent PPH. When analyzed, it was found that both the regimens were equally effective in the prevention of PPH in postoperative CD women. Both the treatment regimens were associated with similar amount of blood loss during the operative and postoperative period. Thus, low-dose oxytocin regimen is as effective as high-dose oxytocin regimen in the prevention of PPH in postoperative CD women.
It is well known that the concentration of oxytocin receptors in uterus keeps on increasing throughout the pregnancy and reaches a peak at term. The concentration of oxytocin receptors is approximately 80 times higher in a pregnant uterus at term as compared to a nonpregnant uterus. In addition, the sensitivity of uterus to oxytocin increases at the onset of labor. Given these statistics, the findings of our study are not surprising wherein a low dose of oxytocin might be able to achieve the same degree of uterine contraction but at expense of fewer side effects than high dose of oxytocin.
It is a usual clinical practice to use higher doses of oxytocin with the belief that higher doses of oxytocin will be able to achieve better uterine contraction. However, once an optimal number of oxytocin receptors are occupied, further increment in the dose of oxytocin is only going to increase the incidence and severity of side effects without any benefit in the amount of uterine contraction. It has been shown earlier that small bolus doses of oxytocin (0.5–3 IU) are associated with adequate uterine contractions and increasing the dose to more than 5 IU increases the incidence of hypotension without any benefits in uterine contraction. In addition, it has been shown both in vitro and in vivo studies that continuous use of oxytocin for approximately 4.2 h may result in desensitization of uterine oxytocin receptor to oxytocin. Thus, continuous infusion of oxytocin beyond this period may not be helpful in maintaining uterine contractions.,, The findings of our study are consistent with seminal work done by these authors.
| » Conclusions|| |
Our study proved the point that a low-dose oxytocin regimen is as good as high-dose regimen in the prevention of PPH in women undergoing CD. The main strength of our study was a uniform treatment protocol as the study was conducted in a single center and an appropriate sample size. The main limitation of this study was that we did not look systemically at the incidence and frequency of side effects related to high-dose oxytocin as the study was designed primarily to look for the efficacy of low-dose oxytocin in the prevention of PPH. The future randomized controlled trials concentrating on both efficacies as well side effect profile of low-dose oxytocin regimens may help in achieving uniform oxytocin dosing protocols for the prevention of PPH.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]