European Journal of Cardiovascular Medicine

Obstetric haemorrhage is one of the most dreaded complications of child birth. While Postpartum haemorrhage is traditionally defined as loss of 500 ml of blood during normal vaginal delivery and 1000 ml during caesarean section, the current definition by the American College of Obstetrics and Gynecology defines it as a cumulative blood loss of 1000 ml regardless of the route of delivery or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours of birth. (1) Postpartum haemorrhage accounts for 38% of maternal deaths in India.(2)The high prevalence of anaemia in the parturient population exacerbates the effects of blood loss during normal vaginal delivery and Caesarean section. Adequate measures to reduce intraoperative blood loss are hence crucial.

Uterine atony remains the most common cause of postpartum haemorrhage. In addition to the normal hemostatic apparatus of the body, postpartum hemostasis also involves the release of endogenous uterotonic agents that contract the uterus and constrict the uterine vessels. Oxytocin and prostaglandins servethis purpose. A failure of this process inadvertently leads to uterine atony and subsequent haemorrhage.

The WHO Technical Working Group and ACOG recommend active management of the third stage of labour which includes uterine massage, umbilical cord traction, and prophylactic administration of uterotonic drugs for the prevention of PPH. (3,4)

Oxytocin is the most common uterotonic drug in use. Exogenous oxytocin has been used for both antepartum and postpartum indications. An effective cold chain is necessary to preserve the efficacy of oxytocin, as it is heat-sensitive. This might pose a problem in less economically developed countries and remote areas.

Carbetocin is a newer oxytocin analogue with a longer half-life. It has recently gain edtractionasan alternative to oxytocin as auterotonic in AMTS Lowing to its heat stability and longer half-life.

This study is an attempt to compare various effects of oxytocin administered as a combination of bolus dose and infusion vs a single bolus dose ofcarbetocin given intra operatively as auterotonic agent for elective LSCS under spinal anaesthesia.

Aims

To compare “The hemodynamic effects of 5 units IV bolus + 10 units IV infusion of Oxytocin vs single IV bolus dose of 100 micrograms Carbetocin administered in parturients undergoing elective Caesarean section under spinal anaesthesia.”

OBJECTIVES

Tostudyand compare

• Effects on Heart Rate
• effects on Systolic blood pressure, diastolic blood pressure and mean arterial pressure.
• Adequacy of Uterine tone
• Incidence of adverse effects–Nausea, vomiting, flushing, chestpain.

Study Setting

Siddhartha Medical College, Government General Hospital, Vijayawada

Study Design: Prospective randomized controlled double-blind study

Study Population

Full-term parturients of age18 to 40 of ASAII undergoing elective Caesarean section under spinal anaesthesia

Study period:

January 2023 to June2024

Inclusion Criteria:

Full term parturients of age 18 – 40 years of ASA grade II undergoing elective caesarean section under spinal anaesthesia.

Exclusion Criteria:

• Refusal to give written informed consent.
• Known allergy or hypersensitivity to carbetocin or oxytocin.
• Patients in labour who were already given Oxytocin
• Need for general anaesthesia
• Multiple gestations, polyhydramnios and foetal anomalies
• ASA grade III and ASA grade IV

After receiving institutional ethical committee approval, 100 full-term parturients of age18–40 years of ASA II aged18–40 who underwent caesarean section under spinal anaesthesia were included in the study.

Written and informed consent were obtained, and patients were randomly divided into two groups, each consisting of 50 patients.

Group O: 5 units IV bolus+10unitsIV infusion of Oxytocin in 500ml NS

Group C: Single IV bolus dose of 100 Microgram of Carbetocin+ 2ml NS added to 500 ml NS

Either one of the drugs was administered based on the randomization after delivery of the right shoulder of the baby. The baseline heart rate, systolic, diastolic,diastolic and mean arterial pressure were noted.

The heart rate, systolic diastolic, and mean arterial pressure at 1 minute, 5 minutes, 10 minutes and 30 minutes after starting the test drug were recorded for all patients Obstetrician was requested to assess uterine to neat 5minutes10 minutes and 30 minutes

By using a 5-point scale 1: Atonic 2: Partial but inadequate contraction 3: Adequate contraction 4: Well-contracted 5: Very well contracted

Alternate uterotonic agents, misoprostol tablets 200 mcg and carboprost, were kept ready for administration at 10 and 15 minutes, respectively, to be administered on request. The patient was no longer a part of the study after administration of additional uterotonic agents.

DEMOGRAPHIC DISTRIBUTION OF CONTROL AND STUDY GROUP

Table 1: Comparison of Age between Study Groups (N=100)

The mean ages in groups O and C were 23.78 and 23.06 years, respectively. The 2 groups did not differ significantly with respect to their age.

Table 2: Comparison of Comorbidities between Study Groups (N=100)

In a comparison of comorbidities between the Carbetocin and Oxytocin groups (each n=50):

• The Carbetocin group had 6% with HO, 2% with GDM, and 2%with pre-
• The Oxytocin group had 2% with FA and 4%with
• The majority in both groups had no comorbidities (90% in Carbetocin, 94% in Oxytocin).

Table 3: Comparison of Parity Between Study Groups

Table 4: Distribution of gestational age between 2 study groups

The mean gestational age in groups O and C was 38.96 and 38.94 weeks, respectively, signifying that the 2 groups had no significant difference with respect to the gestational age of participants enrolled in the study.

Table 5: Comparison of Heart Rate between Study Groups (N=100)

At 1 minute and 5 minutes, the Oxytocin group has significantly higher heart rates compared to the Carbetocin group.

No Significant Differences: At 0 minutes, 10 minutes, and 30 minutes, there are no statistically significant differences in heart rates between the two groups.

Trends: The data suggests that Oxytocin may cause a transient increase in heart rate shortly after administration, which seems to normalise by 10 and 30 minutes.

Table 6: Comparison of SBP between Study Groups (N=100)

Significant difference: At 10minutes, Oxytocin group has a significantly lower SBP than Carbetocin group.

No significant differences: SBP at 0, 1, 5, and 30 minutes shows no significant difference between groups.

Trend: Oxytocin group shows a transient decrease in SBP at 10 minutes, normalizing by 30 minutes.

Table 7: Comparison of DBP between Study Groups (N=100)

Significant difference: At 10minutes,the Oxytocin group has a significantly  lower DBP.

No significant differences: DBP at 0,1,5, and 30 minutes shows no significant difference between groups.

Trend:  Oxytocin causes a transient decrease in DBP at10 minutes, which normalises by 30 minutes.

Table 8: Comparison of MAP between Study Groups(N=100)

Significant difference: At 10minutes, the Oxytocin group had a significantly lower MAP compared to the Carbetocin group.

No significant differences: MAPat0,1,5, and 30 minutes showed no significant difference between the groups.

Trend: The Oxytocin group experienced a transient decrease in MAP at 10 minutes, which normalized by 30 minutes.

Table 9: Comparison of Use of Vasopressors between Study Groups (N=100)

Significant difference: Between 10and 30minutes, the Oxytocin group had significantly higher vasopressor use compared to the Carbetocin group.

No significant differences: Vasopressor use was comparable between the groups in the first 5 minutes and between 5 to 10 minutes.

Table 10: Comparison o f Uterine Tone between Study Groups (N=100)

Table 11: Comparison of Adverse Effects between Study Groups (N=100)

In the present study, There were no reports of flushing in either group. There is no statistically significant difference in the incidence of nausea/vomiting between the two groups

Uterotonics are crucial in AMTSL. Oxytocin is the most widely used first-line uterotonic, endorsed by multiple official bodies. Carbetocin, an oxytocin analogue, has gained popularity due to its heat-stable nature and longer duration of action, which potentially reduces the requirement for prolonged oxytocin infusion.

A comparison between the effects oxytocin and carbetocin serve the purpose of formulating an effective first-line prophylactic treatment protocol for AMTSL. Institutional protocols are variable. There is no consensus even among international bodies regarding the optimal dose of oxytocin, but the recommended dosage of carbetocin has been fairly consistent.

The presence of a stable hemodynamic profile is what would facilitate the incorporation of carbetocinin to the repertoire of first-line drugs for AMTSL in an institution.

The haemodynamic properties that were observed included heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure after administration of either carbetocin or oxytocin. In this study, a significant increase in heart rate was observed in patients within the first 5minutes after Receiving oxytocin, as opposed to a fairly stable heart rate in those who received carbetocin.

A meta-analysis by Leung et al. (2018) (4) of various randomised controlled trials confirmed that oxytocin was linked to a higher incidence of tachycardia than carbetocin in women having caesarean sections.These studies collectively suggest that carbetocin might be a safer option than oxytocin in terms of minimising the risk of tachycardia during caesarean sections. Though both oxytocin and carbetocin were administered in bolus doses, significant tachycardia was observed more frequently with oxytocin.

The changes in systolic blood pressure after administration of either of the drugs were studied. The base line and early response showed no significant difference in SBP between the Carbetocin and Oxytocin groups at baseline (0 minutes ) and at 1 minute. A significant decrease in blood pressure was noticed at the 5 minute time frame with oxytocin when compared to Carbetocin. The same trend was observed at the 10 minutes mark with the Oxytocin group still showing a significantly lower SBP. Yet, At 30 minutes, The difference in SBP between the two groups was no longer statistically significant.

The effects of carbetocin and oxytocin on diastolic blood pressure (DBP)post- administration showed no significant difference in DBP immediately within 1 minute of administration. A similar trend was followed until the 5-minute mark. 10 minutes post-administration, a significant drop in DBP blood pressure was observed in patients who received oxytocin. A significant Drop in SBP was also noticed. Vasopressors were used to normalize blood pressure for a time frame of 10 to 30 minutes. The DBP normalized towards 30 minutes post- administration, and there were no significant differences in DBP in carbetocin and oxytocin .

The comparison between changes in mean arterial blood pressure (MAP) after administering carbetocin and oxytocin also revealed a trend similar to that observed in +DBP. There was no significant difference inchange in MAP within 5 minutes after administration of either of the drugs. A significant fall in MAP was observed in Oxytocin at 10 minutes. This gradually normalised and the MAP between Carbetocin and oxytocin had no significant difference at 30 minutes. In this study, the frequency of use of vasopressors was not significant in the carbetocin or oxytocin group until 10 minutes after administration. A significant difference was noticed from 10 to 30 minutes in the oxytocin group.

Studies comparing carbetocin and oxytocin in caesarean sections have demonstrated similar hemodynamic effects. Both medications are associated with a decrease in blood pressure and an increase in cardiac output and stroke volume. Administering oxytocin and carbetocin produced similar changes in hemodynamics; both drugs decreased mean blood pressure and total vascular resistance while increasing cardiac output and stroke volume, with no marked differences. Carbetocin offered considerable hemodynamic stability, similar to oxytocin, indicating its potential suitability for patients at increased risk of bleeding, such as those with preeclampsia.[6,7](8,9)

In a randomized controlled trial conducted by Bahr et.al 2017(5) hemodynamic responses were assessed in preeclamptic women undergoing elective cesarean sections under spinal anesthesia. Group are ceived Oxytocin

5 IU as an IV bolus dose over 10 seconds in 10 ml 0.9% NaCl solution, and groupB  received carbetocin 100 µg as an IV bolus dose over 10 seconds in 10 ml 0.9% NaCl solution. The study found that both drugs caused a decrease in blood pressure and an increase in heart rate, with these changes being more pronounced in the oxytocin group. Carbetocin showed a safer hemodynamic profile, with blood pressure normalizing within 15 minutes, unlike oxytocin. Furthermore, oxytocin's rapid administration is linked to increased cardiac output and significant hypotension, which could pose risks to patients with cardiovascular issues or hypovolemia. In contrast, carbetocin's effects were more stable, suggesting it might be a safer alternative for preventing postpartum hemorrhage, especially in high-risk patients.

The most common adverse effects attributed to the use of Oxytocics were flushing, nausea, vomiting, and chest pain. This study compared the incidence of these adverse effects between the two drugs. No significant difference was noted in the occurrence of flushing in either study group. While nausea and vomiting were slightly higher in the Carbetocin group in absolute value, the difference was not deemed statistically significant. Chest pain was only observed in patients who received oxytocin but was statistically insignificant.

In a study by Mannaerts et al. (2018) (10), the primary outcome measured was the incidence of adverse effects other than hypotension after administration of oxytocin and carbetocin. That study concluded that a significant difference could not be established regarding the occurrence of the above-mentioned adverse effects, which is in concordance with the findings of this study.

The data suggest that carbetocin is more effective than oxytocin in maintaining optimal uterine tone at critical time points post-cesarean, potentially improving clinical outcomes by reducing the risk of postpartum haemorrhage and supporting faster recovery.

Carbetocin shows a more stable hemodynamic profile in comparison to Oxytocin . Carbetocin has more potent and extended period of adequate uterine tone in comparision with Oxytocin.

Conflict of Interest: None

Funding Support: Nil

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