carbetocin and Hypotension

Carbetocin, an oxytocin analog, given as a postpartum hemorrhage prophylaxis in elective Cesarean deliveries, frequently causes tachycardia and hypotension. Phenylephrine infusion has been shown to prevent spinal anesthesia-induced hypotension. The goal of this study was to evaluate if a slow infusion of carbetocin would reduce maternal heart rate variation and hemodynamic disturbances compared with a rapid bolus in parturients receiving a prophylactic phenylephrine infusion during elective Cesarean delivery.. In this double-blinded randomized controlled trial, 70 healthy parturients were allocated to either a bolus group or an infusion group. At cord clamping, participants in the bolus group received carbetocin 100 µg as a rapid intravenous bolus, while participants in the infusion group received carbetocin 100 µg over 10 min. The primary outcome was the variation in maternal heart rate from baseline during the 20 min following cord clamping. Secondary outcomes included blood pressure, cardiac output, and stroke volume variations during the study period, measured with the ClearSight™ hemodynamic monitor.. Maximum heart rate variation was not different between the groups: bolus group, mean (standard deviation) 29.8 (25.2)% vs infusion group, 27.2 (23.3)%; P = 0.67. The increase in heart rate occurred significantly earlier in the bolus group than in the infusion group (median [interquartile range] time, 105 [69-570] sec vs 485 [255-762] sec; P = 0.02; group × time interaction: two-way repeated measures ANOVA, P = 0.04). There was no significant difference in maximum variations for the other hemodynamic parameters between the groups.. Carbetocin infused over ten minutes did not reduce the magnitude of maternal heart rate variation but delayed its occurrence. This finding could be relevant to the anesthesiologist caring for parturients in whom a slight increase in maternal heart rate is clinically undesirable.. www.. gov (NCT03404544); registered 19 January 2018.. RéSUMé: OBJECTIF: Lorsque la carbétocine, un analogue de l’ocytocine, est administrée à titre de prophylaxie pour les hémorragies du post-partum dans les accouchements par césarienne programmée, cet agent provoque fréquemment une tachycardie et une hypotension. Il a été démontré qu’une perfusion de phényléphrine prévenait l’hypotension induite par la rachianesthésie. L’objectif de cette étude était d’évaluer si une perfusion lente de carbétocine réduirait la variation de fréquence cardiaque maternelle et les perturbations hémodynamiques par rapport à un bolus rapide chez les parturientes recevant une perfusion prophylactique de phényléphrine pendant un accouchement par césarienne programmée. MéTHODE: Dans cette étude randomisée contrôlée à double insu, 70 parturientes en bonne santé ont été allouées à un groupe bolus ou à un groupe perfusion. Lors du clampage du cordon, les participantes du groupe bolus ont reçu 100 μg de carbétocine sous forme de bolus intraveineux rapide, tandis que les participantes du groupe perfusion ont reçu 100 μg de carbétocine sur dix minutes. Le critère d’évaluation principal était la variation de la fréquence cardiaque maternelle par rapport aux valeurs de base au cours des 20 minutes suivant le clampage du cordon. Les critères secondaires comprenaient la tension artérielle, le débit cardiaque et les variations du volume d’éjection au cours de la période d’étude, tels que mesurés avec le moniteur hémodynamique ClearSight™. RéSULTATS: La variation maximale de fréquence cardiaque n’était pas différente entre les groupes : groupe bolus, moyenne (écart type) 29,8 (25,2) % vs groupe perfusion, 27,2 (23,3) %; P = 0,67. L’augmentation de la fréquence cardiaque s’est produite significativement plus tôt dans le groupe bolus que dans le groupe perfusion (temps médian [écart interquartile], 105 [69-570] sec vs 485 [255-762] sec; P = 0,02;× interaction groupe x temps : ANOVA bidirectionnelle à mesures répétées, P = 0,04). Il n’y avait pas de différence significative dans les variations maximales pour les autres paramètres hémodynamiques entre les groupes. CONCLUSION: La carbétocine perfusée pendant dix minutes n’a pas réduit l’ampleur de la variation de la fréquence cardiaque maternelle, mais a retardé son apparition. Cette découverte pourrait être pertinente pour l’anesthésiologiste qui prend soin de parturientes chez qui une légère augmentation de la fréquence cardiaque maternelle serait cliniquement indésirable. ENREGISTREMENT DE L’éTUD

Topics: Anesthesia, Spinal; Double-Blind Method; Female; Heart Rate; Humans; Hypotension; Infusions, Intravenous; Oxytocin; Phenylephrine; Pregnancy; Vasoconstrictor Agents

The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED95) undergoing elective Cesarean delivery under spinal anesthesia.. One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 μg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects.. Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin.. In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 μg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 μg. This trial was registered at www.clinicaltrials.gov (NCT01428817).

Topics: Adult; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypotension; Incidence; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome; Uterine Contraction

The primary objective of our study was to determine the minimum intravenous dose of carbetocin required to produce adequate uterine contraction in 95% of women (effective dose [ED](95)) undergoing elective Cesarean delivery (CD).. Eighty term pregnant women with low risk for postpartum hemorrhage (PPH) undergoing elective CD under spinal anesthesia were randomly allocated to receive carbetocin intravenously in doses of 80 μg, 90 μg, 100 μg, 110 μg, or 120 μg upon delivery. The consultant obstetrician evaluated the efficacy of the patient's uterine tone as satisfactory or unsatisfactory. In case of unsatisfactory uterine tone, additional uterotonics were administered as per routine institutional practice. Side effects were monitored during the study period. The main outcome measure was satisfactory uterine tone at two minutes after carbetocin administration.. Satisfactory uterine tone was obtained in 70 subjects (87%) within the dose range of 80-120 μg of carbetocin. It was not possible to calculate the ED(95) of carbetocin due to the even distribution of women with satisfactory uterine tone across all dose groups (P = 0.99). Similarly, the side effects were similar across all dose groups. There was a high overall incidence of hypotension (55%) following the administration of carbetocin.. In women at low risk for PPH undergoing elective CD, carbetocin doses of 80-120 μg are similarly effective. There is a high incidence of hypotension associated with carbetocin in these doses, and further studies with doses lower than 80 μg are warranted to assess the balance of efficacy and side effects. This trial was registered at www.clinicaltrials.gov (NCT01262742).

Topics: Adult; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypotension; Infusions, Intravenous; Oxytocics; Oxytocin; Pregnancy; Treatment Outcome; Uterine Contraction

Oxytocin and its analogue carbetocin are uterotonics whose prophylactic use is recommended to prevent postpartum haemorrhage, which is one of the leading causes of maternal deaths worldwide. However, both drugs can cause specific adverse effects and haemodynamic challenges.. The aim of this work was to exploratively examine reports of adverse drug events of both drugs and to establish a comparative haemodynamic profile.. Using data extracted from the World Health Organization's pharmacovigilance database VigiBase, a descriptive analysis was performed of all reports for oxytocin and carbetocin as a suspected or interacting drug followed by a disproportionality analysis for haemodynamic events. Reporting odds ratios (ROR) of carbetocin for hypertension, hypotension, tachycardia, and bradycardia were calculated, with oxytocin-related reports serving as comparators.. Oxytocin and carbetocin were mentioned as suspected or interacting drugs in 11,258 and 374 reports, respectively. Resulting RORs for carbetocin were 3.45 (95%CI: 1.72-6.92) for hypertension, 2.65 (1.64-4.28) for hypotension, 2.84 (1.79-4.49) for tachycardia, and 2.00 (0.87-4.60) for bradycardia, when compared to oxytocin. Of 231 patients for whom oxytocin-related tachycardia was reported, 2.6% died, and of 91 patients for whom bradycardia was reported, 2.2% died. No deaths were reported with carbetocin for any of the haemodynamic adverse events.. Compared to oxytocin, carbetocin showed an elevated reporting for adverse hypertension, hypotension, and tachycardia in pharmacovigilance data. Clinicians should be aware of their patients' individual susceptibility and the possibility of haemodynamic deterioration until causal inferences are possible.

Topics: Bradycardia; Drug-Related Side Effects and Adverse Reactions; Female; Hemodynamics; Humans; Hypertension; Hypotension; Oxytocics; Oxytocin; Pharmacovigilance

To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term.. Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM).. All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg.. The MTD was calculated to be at 200 microg carbetocin.

Topics: Abdominal Pain; Female; Humans; Hypertension; Hypotension; Injections, Intramuscular; Oxytocics; Oxytocin; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Vomiting