Side‐effects of carbetocin to prevent postpartum hemorrhage: A systematic review and meta‐analysis of randomized controlled trials

Ai, Wen; Zeng, Yanfei; Ma, Yubo; Liu, Li; Fan, Dazhi; Wu, Song; Zhang, Yinghui

doi:10.1002/prp2.745

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…Importantly, OT‐R are required for CTA development as the OT‐R blockade reduces acquisition of taste aversion and blunts responsiveness of amygdala neurons to an aversive stimulus in mice 29 . The current data are also in line with the clinical reports indicating nausea and emesis after OT infusions in women 25,59‐67 . For women receiving iv injections of oxytocin, pitocin, or carbetocin during labour, nausea and vomiting are common side effects, as noted by many studies 59‐67 …”

Section: Discussionsupporting

confidence: 83%

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects

Asker

Krieger

Liles

et al. 2023

Diabetes Obesity Metabolism

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Objectives: Oxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation.Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure. Methods and Results:We first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IPinjected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B 12 (fCy5-OT-B 12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBBimpermeable OT (OT-B 12 ), with equipotent binding at OT-R in vitro. In vivo, IPinjected OT and OT-B 12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B 12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B 12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression.

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Section: Discussionsupporting

confidence: 83%

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects

Asker

Krieger

Liles

et al. 2023

Diabetes Obesity Metabolism

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“…But in their study Ai et al, suggested that Carbetocin might be considered an appropriate choice for pregnant women with vomiting intolerance for the prevention of PPH, because on their study demonstrated that the administration of Carbetocin in delivery is associated with a lower incidence of vomiting. (14) Carbetocin should not be used in patients with a history of hypersensitivity to oxytocin or Carbetocin, patients with vascular disease, and Carbetocin are intended for use in children. (15)…”

Section: Discussionmentioning

confidence: 99%

Carbetocin: The New Preferred Treatment For Partum Hemorrhage

Martilova¹,

Ushbah

Perdana

2022

ijmsci

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Background: Postpartum hemorrhage defined as the condition blood loss more than 500 mL from the female genital tract after vaginal delivery of the fetus (or >1000 mL after cesarean section). Case Presentation: Mrs. FA 31 year’s old G2P1A0 40 weeks age gestation preeclampsia with main complaints dyspnea and swollen legs. Physical examination showed decreased saturation, increase blood pressure, rhonci, and pitting edema of the pedal. Cardiomegaly with pulmonary edema on x-ray, elevated liver enzymes, LEA value +3, perfectly compensated respiratory alkalosis and electrolyte imbalance on laboratory test. Four-hour post C-section she got postpartum hemorrhagic and given oxytocin due to maximizing use of uterotonic agent, MgSO4 stopped and patient reported with postpartum eclampsia. Conclusion: Many studies discus other drugs to replace oxytocin, considering side effects to prevent postpartum hemorrhage. Carbetocin could be one potent agent of uterotonic agents with lower side effect.

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“…Similar to oxytocin, carbetocin has a prominent vasodilatory effect and, if given too quickly, can cause significant hypotension. A systematic review of adverse effects of carbetocin (17 trials, 32 702 participants) identified 24 adverse effects, of which vomiting, nausea, headache and flushing were the most common 6. Other adverse effects that were less commonly reported included shivering, heart disorders, dizziness, dyspnoea and pruritis.…”

Section: About Carbetocinmentioning

confidence: 99%

Is there a role for carbetocin in the prophylaxis of postpartum obstetric haemorrhage?

Day

Barclay

Page

2022

DTB

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Postpartum haemorrhage is a common complication of pregnancy, most commonly due to uterine atony. Uterotonics have a vital role in preventing postpartum haemorrhage but the choice of the most effective agent with the fewest adverse effects is a subject of debate. Carbetocin, a synthetic analogue of oxytocin has been available in the UK since 2007 but is not currently widely used. It has a longer duration of action than oxytocin, which avoids the need for an infusion and as it is heat-stable it can be stored at room temperature. Current UK clinical guidelines, based on the results of older meta-analyses, do not recommend carbetocin as a first-line agent. A Cochrane review, published in 2018, ranked carbetocin in the top three drug regimens for preventing postpartum haemorrhage and an international consensus statement on uterotonic use for caesarean birth concluded that carbetocin may become the preferred drug for caesarean birth, by reducing the need for additional uterotonics. The higher cost of carbetocin when compared with oxytocin is a limiting factor, but the significant healthcare costs of a postpartum haemorrhage and the physiological impact of this event suggests it a reasonable alternative to consider, especially if ergometrine is contraindicated or in those who are undergoing a caesarean birth or are at high risk of bleeding.

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Side‐effects of carbetocin to prevent postpartum hemorrhage: A systematic review and meta‐analysis of randomized controlled trials

Cited by 15 publications

References 32 publications

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects

Carbetocin: The New Preferred Treatment For Partum Hemorrhage

Is there a role for carbetocin in the prophylaxis of postpartum obstetric haemorrhage?

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