Cardiovascular effects of oxytocin and carbetocin at cesarean section. A prospective double-blind randomized study using noninvasive pulse wave analysis

Abstract

Background

Oxytocin is routinely administered after delivery for prophylaxis and treatment of postpartum hemorrhage, but it is associated with considerable cardiovascular side-effects. Carbetocin, a synthetic oxytocin analogue, has a myometrial contraction effect of 60 min when given IV, compared with 16 min for oxytocin.

Objective

To investigate whether there are differences in cardiovascular effects between oxytocin and carbetocin up to 1 h after treatment.

Methods

Sixty-one healthy pregnant women undergoing elective cesarean section in spinal anesthesia were randomized to receive an IV bolus of either five units (8.3 µg) of oxytocin or 100 µg of carbetocin after delivery of the baby. Heart rate (HR), mean arterial blood pressure, ECG ST index, oxygen saturation (SaO₂), and photoplethysmographic digital pulse wave analysis variables were recorded before and at 1, 5, 20, and 60 min after drug administration. Vasopressor use, uterine tonus, total bleeding, and need for additional uterotonics were also assessed. Repeated measurement ANOVA was used for statistical analyses.

Results

The drugs had equal vasodilatory and hypotensive effects. Oxytocin, but not carbetocin, caused a decrease in HR at 1 min and a sustained decrease in cardiac left ventricular ejection time. Aggregate vasopressor use was higher in the carbetocin group. Neither drug caused any change in ST index, SaO₂, or subjective cardiac symptoms. Uterine tonus, need for additional uterotonics, or total bleeding did not differ significantly between the groups.

Conclusion

Single doses of oxytocin and carbetocin had similar dilatory effects on vascular tonus, where the difference in aggregate vasopressor use can be attributed to a more persistent hypotensive effect of carbetocin. A transient negative chronotropic and sustained negative inotropic effect occurred after oxytocin. Neither drug showed any alarmingly adverse effects. Differences in drug effects may be attributed to differences in oxytocin and vasopressin receptor signaling pathways.

Keywords:

• Carbetocin
• cardiovascular effects
• cesarean section
• oxytocin
• pharmacologic effects
• pulse wave analysis

Author contributions

SR: conceptualization, planning, recruiting, performing, statistical analyses, analyzing results, literature search, writing the manuscript. HJ: recruiting, performing, statistical analyses, analyzing results, literature search, reviewing manuscript. EJ: recruiting, performing, statistical analyses, analyzing results, literature search, reviewing manuscript. PO: conceptualization, planning, ethics approval, medical agency approval, statistical analyses, analyzing results, literature search, writing the manuscript.

Disclosure statement

PO was previously Consultant Medical Adviser of Ferring Pharmaceuticals AB, Malmö, Sweden, the manufacturer of carbetocin (Pabal©), but resigned in 2016. The company has not been involved in planning, performance or supporting the study. SR, HJ and EB declare no conflicts of interest.

Additional information

Funding

The study was funded by grants from the Medical Faculty at Lund University (ALF) and Region Skåne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.