European Journal of Cardiovascular Medicine

Postpartum haemorrhage accounts for up to 30% of maternal fatalities globally, making it one of the leading causes of maternal mortality. (1) When compared to vaginal delivery, caesarean sections result in significantly higher blood loss, hence efforts should be taken to minimise the blood loss. The World Health Organisation advises using uterotonics to avoid PPH in all births during the third stage of labour; Oxytocin 10 IU IM/IV is the recommended medication. (2) Oxytocin administered through IV bolus possesses no safety concerns following a vaginal delivery and must be regarded as an appropriate choice for PPH preventative measures. (3) However, there are concerns about the hemodynamic changes associated with bolus dose of oxytocin during caesarean section. Following a caesarean delivery, parturient women may experience hemodynamic abnormalities due to autotransfusion of uterine contraction, haemorrhage, vasoconstriction, effect of anaesthesia and excitement; however, certain investigations have indicated that the primary factor is the uterotonic medication. (4,5)

The most common uterotonic medication used for caesarean sections is oxytocin, which causes peripheral vasodilation, uterine contraction during the procedure, and a drop in arterial pressure following delivery, all of which minimises the bleeding. (6,7)

However, its potent vasodilatory effects can lead to significant hemodynamic changes, including hypotension, tachycardia, circulatory collapse, pulmonary edema owning to oxytocin's antidiuretic effect and death.(8–10) The method of oxytocin administration may influence these hemodynamic responses, impacting patient safety and comfort.(4)  Research claims that bolus with infusion of oxytocin has superior effect over only infusion technique but the hemodynamic variation also more probably owning to the higher dose of the bolus.(11)

Therefore, we hypothesized that a low dose bolus-infusion (2 plus 8 IU) regimen would combine the benefits of both the bolus and infusion with no added side effects.

In this study we aimed to compare the hemodynamic effects of two different administration methods of oxytocin during caesarean section: continuous intravenous injection and bolus plus continuous intravenous injection.

The institutional ethics committee (EC/NEW/INST/2023/KA/0382) clearance was obtained for this randomized clinical trial which was conducted at AIMS hospital BG Nagara, Karnataka. After being informed about the study's purpose, methodology, and any associated risks, written and informed consent was obtained from all parturient with gestational age 38 completed weeks or above scheduled for a planned caesarean section under subarachnoid block. Study featured 30 parturient in each group, achieving a power of 90% and an α error of 5%. Computer-generated randomization was employed and the research participants were split into two groups: Group IB were administered with 2 IU bolus followed by an 8 IU infusion (2 IU given IV over 1 minute and remaining 8 IU added into IV RL and infused at 60 drops/min), and Group I received a 10 IU (10 IU added into IV RL and infused at 60 drops/min) of oxytocin by infusion.

On the day of surgery after preanesthetic evaluation and confirmation of the NPO status the parturient was wheeled into the operating theatre and baseline vitas was recorded with standard ASA monitors. Subarachnoid block was performed using 25G spinal needle with patient in the sitting position in L3-L4 inter-space and location of subarachnoid space was confirmed by free flow of CSF. Immediately after intra-thecal administration of 2ml of 0.5% injection bupivacaine (hyperbaric), the patient was placed in the supine position with a wedge under the right flank to achieve a leftward tilt of 15º and oxygen supplementation at a rate of 5 L/min was started via a face mask.

Surgery was allowed to proceed after loss of sensation to pinprick up to T4 level. After delivery, the predetermined group received their oxytocin injection as prescribed. An

obstetrician, who was the same physician in all of the instances, evaluated the tone of the uterus and determined whether it was adequate or inadequate. Changes in intraoperative heart rate, blood pressure and mean arterial pressure were recorded. The obstetrician gave the uterine contractions a grade on a linear analogue score (LAS) that ranged from 0 to 10 (0 - atonic and 10 - fully contracted). Based on uterine contractions, the surgeon scored the LAS every five minutes for the first 15 minutes. Any ECG changes were monitored. Any adverse reactions like chest discomfort, flushing, and vomiting were also recorded.

2.8: Statistical analysis of data: The data obtained was entered in a Microsoft Excel sheet and analysed using Statistical Package for the Social Sciences (SPSS) for Windows, version 23.0

During the study there was a failure of spinal anaesthesia procedure in 3 patients and was converted to general anaesthesia. While three patients developed significant hypotension and required vasopressor prior to oxytocin administration. But four patients required rescue uterotonic other than oxytocin. Ten patients violated the study protocol thus and were excluded from analysis

Table 1. Demographic data

There was no significant difference in the demographic data with the groups (table 1)

The study monitored hemodynamic parameters such as systolic, diastolic blood pressure and pulse rate indicating a potential difference in the hemodynamic response to the drug between the two groups as shown in the below table. (Table.2)

The mean blood pressure of the two groups was comparable at all times. There was a fall in both systolic and diastolic blood pressures following spinal anaesthesia and at the second minute following oxytocin bolus in both the groups. But the range of fall of both systolic and diastolic blood pressures was similar in both the groups. The systolic blood pressure was lowest at 2 minutes (Group IB :99±10 vs Group I :105±13) following delivery in both the groups and there was no statistically significant difference in the blood pressure between the groups (p<0.05). Similarly ,diastolic blood pressures were also the lowest at 2 minutes (62±9 vs 63±9) following delivery and there was no statistically significant difference in the blood pressure between the groups (p<0.05).A linear decrease in systolic and diastolic blood pressures was observed in both groups with no statistically significant differences between groups .The fall in MAP in bolus group was higher than that in the Infusion Group at all time intervals but showed no statistical significance in MAP between the two groups

                                                Table.2 Blood pressure readings between the two groups

The heart rate increased to a maximum 14 beats/minute in Group IB at 5 minutes (105.4±8) and gradually decreased but did not touch the basal value even after 15 minutes. In case of Group I the maximum heart rate increased by about 7 beats per minute at 5 minutes (99.4±8) of starting infusion, gradually decreased but did not touch the basal value even after 15 minutes. All the values of mean heart rate of bolus group were higher compared to infusion Group and differences were statistically significant at 5 minutes (p=0.018) and 15 minutes (p=0.03).

The increase in Heart rate in bolus group was higher than that in the Infusion Group at all time intervals as seen in Figure .1, and was statistically significant at 5 and 15 minutes.

Table .3 LAS score to assess contraction levels between the two groups

The linear analogue scale (LAS) score was used to assess contraction levels in both Group IB and Group I at 5,10- and 15-minutes interval as shown in the below. (Table 3.3 ) The degree of uterine contraction at 5 and 10 minutes after the injection of oxytocin was significantly higher in groups IB than that in Group I according to the LAS score based on the palpation of the obstetrician (P <0.05).

Hemorrhage was observed in both groups, but the difference between the groups was not statistically significant. The mean hemorrhage in Group IB was 838 ± 35.5ml, while in Group I it was 843 ± 39.6ml.

In the comparison between the two groups, it was observed that Group I had two participants experiencing nausea and vomiting, whereas Group IB had one participant experiencing shivering as a side effect.

All over the world widely varying regimens of oxytocin are being used to prevent blood loss among parturient mothers during caesarean section. The mechanism of action of these regimens also differs; bolus causes constriction of venous sinuses, leading to placental separation and placental bed hemostasis and infusion maintains the uterine tone. Now carbetocin; a synthetic oxytocin with a longer half-life is also preferred in some countries for this purpose, but the high cost restricts its use in resource limited settings, and oxytocin continues to be the drug of choice. (12,13)

In our study, we compared two groups: Group IB received a 2 IU bolus followed by an 8 IU infusion, while Group I received a 10 IU infusion of oxytocin. By analyzing various variables, we aimed to determine the appropriate form of oxytocin administration for cesarean sections.

This research showed no statistically significant difference in Systolic and diastolic blood pressures between the two groups. Both the groups showed a linear fall in Blood Pressures and MAP which was comparable between the two groups with Group IB showing a slightly larger fall than compared to Group I. This finding aligns with Sarna et al.'s study, where they observed a decrease in MAP by 45 mm Hg in a group receiving a rapid bolus of 5U oxytocin only. (14)

Additionally, we noted that at all time intervals, the MAP decline in the bolus group was greater than that in the infusion group with the highest fall following 2 minutes of injecting oxytocin ; nevertheless, there was no statistically significant difference in MAP between the two groups.The fluctuations in MAP induced by oxytocin can be attributed to its effects on endocrine and paracrine pathways, as well as its ability to control coronary perfusion pressure through vasodilation of coronary resistance arteries.(7)

In our study we found that there was a linear increase in Heart rate in both the groups with statistically significant changes seen at 5 minutes and 15 minutes. Group IB showing a slightly higher increase in heart rate than compared to Group I. This aligns with study conducted by J S Thomas's et.al, where the pulse rate was higher in the bolus group compared to the infusion group. (4)  These hemodynamic changes by oxytocin are always temporary and the effect on healthy parturient women is minimal. However, they may be dangerous to parturient women who have underlying cardiovascular diseases or are in hypovolemia. Hence, continuous intravenous injection of oxytocin at a low concentration is primarily recommended as a safe injection method for parturient women in a high-risk group.

In a study by Ayedi et al, concluded that uterine contractions were better in bolus with infusion group when compared to infusion only as assessed by the LAS score. Adequate uterine contractions were achieved faster in the oxytocin bolus group. (15)

Incidence of Hemorrhage was observed in both the groups, but the difference in mean hemorrhage (Group IB:838 ± 35.5ml, Group I:843 ± 39.6ml) was not statistically significant These findings were in contrast with a study conducted by Mathe P et al., where the blood loss was higher in the infusion group (1076.90 ± 241.45 ml) compared to the bolus and infusion group (844.37 ± 189.15 ml).(16) Similarly, in a pilot study by Murphy et al., comparing blood loss in elective lower segment cesarean section (LSCS), the total mean estimated blood loss was lower in the oxytocin "infusion and bolus" group (567 ml) compared to the "only bolus" group (624ml).(17)

Oxytocin is also known to cause certain undesirable effects based on the form of injection. (4) In terms of adverse events, our study observed a low incidence overall. Group I had two participants experiencing nausea and vomiting, while Group IB (bolus and infusion) had one participant with shivering. This aligns with Mohammed M. et al.'s study, where both bolus and infusion group and infusion group had a 6% incidence of nausea and vomiting. (18)

The use of a low dose oxytocin bolus followed by continuous infusion during caesarean sections is a superior strategy for managing hemodynamic parameters. It provides effective uterotonic action with fewer adverse cardiovascular effects, suggesting its adoption as a standard practice in obstetric anesthesia. Further studies with larger sample sizes and varied clinical settings are recommended to corroborate these findings and refine dosing protocols for optimal patient care

1. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014 Jun;2(6):e323-333.
2. WHO Recommendations for the Prevention and Treatment of Postpartum Haemorrhage [Internet]. Geneva: World Health Organization; 2012 [cited 2024 Jul 1]. (WHO Guidelines Approved by the Guidelines Review Committee). Available from: http://www.ncbi.nlm.nih.gov/books/NBK131942/
3. Charles D, Anger H, Dabash R, Darwish E, Ramadan MC, Mansy A, et al. Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial. BMC Pregnancy Childbirth. 2019 Jan 18;19(1):38.
4. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing Caesarean section. Br J Anaesth. 2007 Jan;98(1):116–9.
5. Pinder AJ, Dresner M, Calow C, Shorten GD, O’Riordan J, Johnson R. Haemodynamic changes caused by oxytocin during caesarean section under spinal anaesthesia. Int J Obstet Anesth. 2002 Jul;11(3):156–9.
6. Shyken JM, Petrie RH. The use of oxytocin. Clin Perinatol. 1995 Dec;22(4):907–31.
7. Petersson M. Cardiovascular effects of oxytocin. Prog Brain Res. 2002;139:281–8.
8. Heytens L, Camu F. Pulmonary edema during cesarean section related to the use of oxytocic drugs. Acta Anaesthesiol Belg. 1984 Jun;35(2):155–64.
9. Svanström MC, Biber B, Hanes M, Johansson G, Näslund U, Bålfors EM. Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section. Br J Anaesth. 2008 May;100(5):683–9.
10. Cooper GM, Lewis G, Neilson J. Confidential enquiries into maternal deaths, 1997-1999. Br J Anaesth. 2002 Sep;89(3):369–72.
11. Davies GAL, Tessier JL, Woodman MC, Lipson A, Hahn PM. Maternal hemodynamics after oxytocin bolus compared with infusion in the third stage of labor: a randomized controlled trial. Obstet Gynecol. 2005 Feb;105(2):294–9.
12. Sheehan SR, Montgomery AA, Carey M, McAuliffe FM, Eogan M, Gleeson R, et al. Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial. BMJ. 2011 Aug 1;343:d4661.
13. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin during elective Caesarean delivery. Br J Anaesth. 2010 Mar;104(3):338–43.
14. Sarna MC, Soni AK, Gomez M, Oriol NE. Intravenous oxytocin in patients undergoing elective cesarean section. Anesth Analg. 1997 Apr;84(4):753–6.
15. Ayedi M, Zouche I, Smaoui L, Bouaziz I, Smaoui M, Kolsi K. Comparison of 2 versus 5 units of oxytocin in caesarean section: 11AP2-6. Eur J Anaesthesiol. 2011 Jun;28:159.
16. Mathe P, Kale S, Batra A, Batra A, Aggrawal S, Nagarajappa A. Intravenous oxytocin bolus and infusion versus infusion alone on the blood loss during caesarean section. Int J Reprod Contracept Obstet Gynecol. 2019 Nov 26;8(12):4824.
17. Murphy DJ, MacGregor H, Munishankar B, McLeod G. A randomised controlled trial of oxytocin 5IU and placebo infusion versus oxytocin 5IU and 30IU infusion for the control of blood loss at elective caesarean section—Pilot study. ISRCTN 40302163. Eur J Obstet Gynecol Reprod Biol. 2009 Jan;142(1):30–3.
18. Mahmoud M, El-Garhey I, A. El-Boghdady A. A COMPARATIVE STUDY BETWEEN OXYTOCIN INTRAVENOUS BOLUS VERSUS OXYTOCIN INTRAVENOUS BOLUS AND INFUSION FOR CONTROL OF BLOOD LOSS AT ELECTIVE CESAREAN SECTION. Al-Azhar Med J. 2021 Jan 1;50(1):419–32.