Discussion
flushing, tachycardia, blood loss, chest pain, labor, hypotension, nausea,, PPH, depression, headache, uterine atony
REGRESSION, CONTRACTION, BLOOD LOSS, UTERINE ATONY
In this prospective dose-finding study, we have shown that, in women receiving 0.5 μg/kg/min phenylephrine to prevent post-spinal hypotension during elective cesarean delivery, the ED90 of oxytocin to prevent uterine atony was 9.3 IU/h. This value is significantly higher than the recommended dose by an international consensus statement [Oxytocin is widely used for the prevention of PPH. Various organizations have suggested different protocols for the use of oxytocin during the third stage of labor in cesarean delivery. The Royal College of Obstetricians and Gynaecologists of the UK has recommended 5 IU of oxytocin slowly infused as an i.v. bolus [However, many factors could influence the UT. In Lavoie’s study, it was found that women with prior exposure to exogenous oxytocin required higher infusion doses of oxytocin to maintain UT, in comparison with women without prior exposure (44.2 IU/h vs. 16.2 IU/h) [The strength of the present study is in providing full dose-response information on the oxytocin infusion dose for the prevention of uterine atony. In this study, the calculated ED90 (9.3 IU/h) of the oxytocin infusion dose was higher than the results of Qian’s study. In Qian’s study, it was found, using a very similar probit regression design to ours, that after a bolus of 1 IU oxytocin the ED95 infusion dose of oxytocin was 7.72 IU/h [The exact mechanism through which prophylactic phenylephrine increases the oxytocin dose requirement to prevent uterine atony is still unclear. Nevertheless, there are two potential explanations. First, phenylephrine suppressed uterine contraction in non-pregnant mice, through cyclic adenosine monophosphate (cAMP) signaling via β2-receptor activation [It should be kept in mind that the optimum dose of the initial bolus of oxytocin is still unknown in patients with prophylactic phenylephrine treatment after neonatal delivery. We chose an initial dose regimen of 3 IU rather than 1 IU, (3-fold the dose suggested by the international consensus statement), to reduce the potential higher risk of PPH in patients receiving prophylactic phenylephrine to manage post-spinal blood pressure. In this framework, further studies are needed to determine the optimal initial dose of oxytocin. Notably, we would like to interpret that the estimated blood loss was similar among the four fixed infusion doses of oxytocin, due to the close observation and timely treatment with rescued oxytocin and the second line uterine agent. Hence, the data in this study suggested that the management of oxytocin infusion should be based on patient’s response, because not all patients respond to oxytocin in the same way.It should be noted that oxytocin use is associated with major cardiovascular side effects, including hypotension, ST depression, and tachycardia. Despite seemingly less serious, nausea, vomiting, chest pain, headache, and flushing are additional commonly experienced and unpleasant side effects. After careful literature revision, we found that these side effects are dependent on the dose and the administration rate. A randomized clinical trial has shown that ST depression occurred in 8% of women after a 5 IU oxytocin bolus vs. 22% after 10 IU, which was proved to be related to the occurrence of severe hypotension [There were several limitations in the current study. First, the assessment of UT was subjective. Different obstetricians could have different evaluation criteria for the UT. Second, because of the critical criteria used for patient inclusion and exclusion, the results of the current may not apply to all kinds of patients. In addition, this study only enrolled patients for elective cesarean delivery; therefore, the ED90 value determined might not be applicable to patients under emergency cesarean delivery. Finally, the initial oxytocin dose in this study was 3 IU. Different institutions may use different initial bolus administration doses, which could influence the dose requirement for the subsequent infusion. Thus, further studies are needed to evaluate whether the ED90s of oxytocin infusion are changed when different initial boluses of oxytocin are used.