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      Cost effectiveness analysis of carbetocin during cesarean section in a high volume maternity unit

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          Abstract

          Aim

          To evaluate the cost effectiveness of carbetocin compared to oxytocin when used as prophylaxis against post‐partum hemorrhage (PPH) during cesarean deliveries.

          Methods

          A systematic review of the literature was performed to identify randomized controlled trials that compared the use of carbetocin to oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was then performed using secondary data from the perspective of a maternity unit within the Malaysian Ministry of Health, over a 24 h time period.

          Results

          Seven randomized controlled trials with over 2000 patients comparing carbetocin with oxytocin during cesarean section were identified. The use of carbetocin in our center, which has an average of 3000 cesarean deliveries annually, would have prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need for additional uterotonics in 455 patients. The incremental cost effectiveness ratio of carbetocin for averting an episode of PPH was US$278.70.

          Conclusion

          Reduction in retreatment, staffing requirements, transfusion and potential medication errors mitigates the higher index cost of carbetocin. From a pharmacoeconomic perspective, in the context of cesarean section, carbetocin was cost effective as prophylaxis against PPH. Ultimately, the relative value placed on the outcomes above and the individual unit's resources would influence the choice of uterotonic.

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          Most cited references21

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          Active management of the third stage of labour: prevention and treatment of postpartum hemorrhage.

          To review the clinical aspects of postpartum hemorrhage (PPH) and provide guidelines to assist clinicians in the prevention and management of PPH. These guidelines are an update from the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) clinical practice guideline on PPH, published in April 2000. Medline, PubMed, the Cochrane Database of Systematic Reviews, ACP Journal Club, and BMJ Clinical Evidence were searched for relevant articles, with concentration on randomized controlled trials (RCTs), systematic reviews, and clinical practice guidelines published between 1995 and 2007. Each article was screened for relevance and the full text acquired if determined to be relevant. Each full-text article was critically appraised with use of the Jadad Scale and the levels of evidence definitions of the Canadian Task Force on Preventive Health Care. The quality of evidence was rated with use of the criteria described by the Canadian Task Force on Preventive Health Care. The Society of Obstetricians and Gynaecologists of Canada. Prevention of Postpartum Hemorrhage 1. Active management of the third stage of labour (AMTSL) reduces the risk of PPH and should be offered and recommended to all women. (I-A) 2. Oxytocin (10 IU), administered intramuscularly, is the preferred medication and route for the prevention of PPH in low-risk vaginal deliveries. Care providers should administer this medication after delivery of the anterior shoulder. (I-A) 3. Intravenous infusion of oxytocin (20 to 40 IU in 1000 mL, 150 mL per hour) is an acceptable alternative for AMTSL. (I-B) 4. An IV bolus of oxytocin, 5 to 10 IU (given over 1 to 2 minutes), can be used for PPH prevention after vaginal birth but is not recommended at this time with elective Caesarean section. (II-B) 5. Ergonovine can be used for prevention of PPH but may be considered second choice to oxytocin owing to the greater risk of maternal adverse effects and of the need for manual removal of a retained placenta. Ergonovine is contraindicated in patients with hypertension. (I-A) 6. Carbetocin, 100 microg given as an IV bolus over 1 minute, should be used instead of continuous oxytocin infusion in elective Caesarean section for the prevention of PPH and to decrease the need for therapeutic uterotonics. (I-B) 7. For women delivering vaginally with 1 risk factor for PPH, carbetocin 100 microg IM decreases the need for uterine massage to prevent PPH when compared with continuous infusion of oxytocin. (I-B) 8. Ergonovine, 0.2 mg IM, and misoprostol, 600 to 800 microg given by the oral, sublingual, or rectal route, may be offered as alternatives in vaginal deliveries when oxytocin is not available. (II-1B) 9. Whenever possible, delaying cord clamping by at least 60 seconds is preferred to clamping earlier in premature newborns (< 37 weeks' gestation) since there is less intraventricular hemorrhage and less need for transfusion in those with late clamping. (I-A) 10. For term newborns, the possible increased risk of neonatal jaundice requiring phototherapy must be weighed against the physiological benefit of greater hemoglobin and iron levels up to 6 months of age conferred by delayed cord clamping. (I-C) 11. There is no evidence that, in an uncomplicated delivery without bleeding, interventions to accelerate delivery of the placenta before the traditional 30 to 45 minutes will reduce the risk of PPH. (II-2C) 12. Placental cord drainage cannot be recommended as a routine practice since the evidence for a reduction in the duration of the third stage of labour is limited to women who did not receive oxytocin as part of the management of the third stage. There is no evidence that this intervention prevents PPH. (II-1C) 13. Intraumbilical cord injection of misoprostol (800 microg) or oxytocin (10 to 30 IU) can be considered as an alternative intervention before manual removal of the placenta. (II-2C) TREATMENT OF PPH: 14. For blood loss estimation, clinicians should use clinical markers (signs and symptoms) rather than a visual estimation. (III-B) 15. Management of ongoing PPH requires a multidisciplinary approach that involves maintaining hemodynamic stability while simultaneously identifying and treating the cause of blood loss. (III-C) 16. All obstetric units should have a regularly checked PPH emergency equipment tray containing appropriate equipment. (II-2B) 17. Evidence for the benefit of recombinant activated factor VII has been gathered from very few cases of massive PPH. Therefore this agent cannot be recommended as part of routine practice. (II-3L) 18. Uterine tamponade can be an efficient and effective intervention to temporarily control active PPH due to uterine atony that has not responded to medical therapy. (III-L) 19. Surgical techniques such as ligation of the internal iliac artery, compression sutures, and hysterectomy should be used for the management of intractable PPH unresponsive to medical therapy. (III-B) Recommendations were quantified using the evaluation of evidence guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1).
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            Double-blind comparison of carbetocin versus oxytocin in prevention of uterine atony after cesarean section.

            The goal of this study was to compare carbetocin, a long-acting oxytocin analog, with oxytocin in the prevention of uterine atony after cesarean section. We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter, double-blind, randomized clinical trial. We compared the effect of a single 100 microg dose of carbetocin with that of a standard 8-hour infusion of oxytocin. The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony. A variable sample size, sequential design was used. The overall oxytocic intervention rate was 7.4%. The odds of treatment failure requiring oxytocic intervention was 2.03 (95% confidence interval 1.1 to 2.8) times higher in the oxytocin group compared with the carbetocin group, respectively, 32 of 318 (10.1%) versus 15 of 317 (4.7%), P <.05. Carbetocin, a new drug for the prevention of uterine atony, appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile.
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              Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section: the results of a double-blind randomised trial.

              To compare the effectiveness of carbetocin and oxytocin when they are administered after caesarean section for prevention of postpartum haemorrhage (PPH). Double-blind randomised single centre study (1:1 ratio). Teaching hospital in Bristol, UK with 6000 deliveries per annum. Women at term undergoing elective or emergency caesarean section under regional anaesthesia, excluding women with placenta praevia, multiple gestation and placental abruption. Women were randomised to receive either carbetocin 100 microg or oxytocin 5 IU intravenously after the delivery of the baby. Perioperative care was otherwise normal and use of additional oxytocics was at the discretion of the operating obstetrician. Analysis was by intention to treat. The proportion of women in each arm of the trial that needed additional pharmacological oxytocic interventions. Significantly more women needed additional oxytocics in the oxytocin group (45.5% versus 33.5%, Relative risk 0.74, 95% CI 0.57-0.95). The majority of women had oxytocin infusions. There were no significant differences in the secondary outcomes, including major PPH, blood transfusions and fall in haemoglobin. Carbetocin is associated with a reduced use of additional oxytocics. It is unclear whether this may reduce rates of PPH and blood transfusions.
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                Author and article information

                Contributors
                vhaxyn@gmail.com
                Journal
                J Obstet Gynaecol Res
                J. Obstet. Gynaecol. Res
                10.1111/(ISSN)1447-0756
                JOG
                The Journal of Obstetrics and Gynaecology Research
                John Wiley & Sons Australia, Ltd (Kyoto, Japan )
                1341-8076
                1447-0756
                13 October 2017
                January 2018
                : 44
                : 1 ( doiID: 10.1111/jog.2018.44.issue-1 )
                : 109-116
                Affiliations
                [ 1 ] Department of Obstetrics and Gynecology Sri Aman Hospital Sarawak Malaysia
                [ 2 ] School of Pharmaceutical Sciences University of Science Malaysia Penang Malaysia
                [ 3 ] Clinical Research Centre Sarawak General Hospital Kuching Malaysia
                [ 4 ] Department of Obstetrics and Gynecology Sarawak General Hospital Kuching Malaysia
                Author notes
                [*] [* ]Correspondence: Dr Hian Yan Voon, Department of Obstetrics and Gynecology, Hospital Road Sri Aman Hospital, 95000 Sri Aman, Sarawak, Malaysia. Email: vhaxyn@ 123456gmail.com
                Author information
                http://orcid.org/0000-0001-5269-7565
                Article
                JOG13486 JOGR-2017-0516.R1
                10.1111/jog.13486
                5813149
                29027315
                ca59555f-54d8-4378-8c11-14438e812987
                © 2017 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 05 May 2017
                : 22 July 2017
                Page count
                Figures: 2, Tables: 3, Pages: 8, Words: 4299
                Funding
                Funded by: Persatuan Postgraduat Obstetrik & Ginekologi Sarawak
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                jog13486
                January 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:15.02.2018

                carbetocin,cesarean section,cost effectiveness,pharmacoeconomic,post‐partum hemorrhage

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