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Uterotonic agents for caesarean section Thierry Girard Basel, Switzerland Conflict of interest Medical methods for preventing blood loss at caesarean section (Protocol) Connell JE, Mahomed K This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 1 http://www.thecochranelibrary.com Medical methods for preventing blood loss at caesarean section (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Uterotonic agents for caesarean section • Why ? • Which ? • How ? • When ? Cochrane Reviews 2013, Issue 10. Art. No.: CD001808 Why ? >50 % Uterotonic agents for caesarean section • Why ? • Which ? • How ? • When ? Which ? • Oxytocic • Prostaglandins • Ergot alkaloids Which ? • Oxytocic • Oxytocin • Carbetocin • Prostaglandins • Ergot alkaloids Which ? • Oxytocic • Oxytocin • Carbetocin • Prostaglandins • PGE1: misoprostol • PGE2: dinoprostone, prostin, sulprostone • PGF2�: dinoprost, carboprost, hemabate • Ergot alkaloids Which ? • Oxytocic • Oxytocin • Carbetocin • Prostaglandins • PGE1: misoprostol • PGE2: dinoprostone, prostin, sulprostone • PGF2�: dinoprost, carboprost, hemabate • Ergot alkaloids • Methylergometrine, methergine Uterotonic agents for caesarean section • Why ? • Which ? • How ? • When ? Int J Obstet Anesth (2010) 19:313–319. How ? Ca2+ Calmodulin MLCK IP3 Myometrial Ca2+ contraction Ca2+ PG synth PIP2 IP3 R G ER PLC DAG Which ? • Oxytocin • Prostaglandins • Ergot alkaloids Oxytocin • Adverse effects • Receptor desensitisation • Down regulation Oxytocin - adverse effects • Cardiovascular • Hypotension • Arrhythmias • Myocardial ischemia • Increased pulmonary artery pressure • Nausea & vomiting • Headache • Flushing J. Phy8iol. (1965), 178, pp. 563-576 563 With 5 text-figture.s Printed in Great Britain A RELATIONSHIP BETWEEN ADRENALINE AND THE MODE OF ACTION OF OXYTOCIN AND OESTROGEN ON VASCULAR SMOOTH MUSCLE BY A. L. HAIGH, SYBIL LLOYD AND MARY PICKFORD From the Departments of Veterinary Physiology, and of Physiology, The University, Edinburgh (Received 30 October 1964) Papers already published report that in the normal mammals so far examined (man, dog and rat, both sexes) oxytocin dilates a number of vascular beds (Lloyd, 1959a, b; Lloyd & Pickford, 1961; see Haigh, Kitchin & Pickford, 1963). This dilator effect is converted to a constrictor one following chemical blockage of ganglia or peripheral sympathetic nerves, after surgical sympathectomy of the part, and after administra- tion of reserpine. The same change is also induced by subcutaneous or intravenous administration of oestrogens, or when the animal (rat) is in natural oestrus. As a first step towards elucidating the mechanism of the identical change in the response to oxytocin induced by procedures as diverse as oestrogen administration and interference with the sympathetic nervous system, it was decided to attempt restoration of the dilator effect of oxytocin after having caused the appearance of the constrictor one. This paper is chiefly concerned with experiments made to this end on a number of dogs and on two monkeys. Brief reference to some of these results has already been made (Haigh, Lloyd & Pickford, 1964; Pickford, 1964). METHODS The observations were made on a number of dogs of both sexes and on two female monkeys. All but two of the experiments were acute ones in which the animals were anaesthetized with pentobarbitone, 26 5 mg/kg body weight, given intravenously; the animals also received heparin, 5 mg/kg body weight intravenously. Mean blood pressure was recorded by mercury manometer from the carotid artery. Blood flow through the hind limb was measured by means of a Pavlov (1887) stromuhr inserted between the cut ends of the femoral vein. When preparations were complete a period of 25-40 min was allowed before observations were begun. Chronic observations were made in one female and one male dog and, in these, leg flow was measured by means of venous occlusion plethysmography. The diaphragm of the plethysmograph was specially designed with an irregular ovoid opening shaped like the cross-section of a dog's leg. The leg was inserted through this into a thin rubber bag made of two breadths of 2 in. diameter colostomy tubing sealed together; in the usual way the rubber bag was attached to the rim of the diaphragm across the opening of the plethysmograph. 36-2 DOI: 10.1111/j.1471-0528.2009.02356.x General obstetrics www.bjog.org BJOG. 2010;117(9):1165–6. ST depression at caesarean section and the relation to oxytocin dose. A randomised controlled trial M Jonsson,a U Hanson,a C Lidell,b S Norde´ n-Lindeberga a Department of Women’s and Children’s Health Uppsala University, Uppsala, Sweden b Department of Clinical Physiology Uppsala University Hospital, Uppsala, Sweden Correspondence: M Jonsson, Department of Women’s and Children’s Health, Uppsala University, SE-751 85 Uppsala, Sweden. Email [email protected] Accepted 21 July 2009. Published Online 14 September 2009. Objective To investigate whether there is a difference Results There was a significant difference in occurrence of ST in occurrence of electrocardiogram changes suggestive depressions associated with oxytocin administration, 4 (7.7%) of myocardial ischaemia between two different doses of with 5 and 11 (21.6%) with 10 units, P < 0.05. The absolute risk oxytocin. reduction was 13.9% (95% confidence interval, 0.5–27.3). Decrease of mean MAP from baseline to 2 minutes differed, being Design Double-blind randomised controlled trial 9 mmHg in the 5 unit group and 17 mmHg in the 10 unit group Setting University hospital in Sweden. (P < 0.01). The increase in mean HR did not differ. Troponin I levels were increased in four subjects (3.9%). There were no Population A total of 103 healthy women undergoing elective differences in occurrence of symptoms, Troponin I levels, or caesarean section under spinal anaesthesia. estimated blood loss. Methods The participants were randomised to 5 or 10 units of Conclusion ST depressions were associated with oxytocin oxytocin, given as an intravenous bolus. A Holter monitor was administration significantlynobody more often in subjects uses receiving 10 U used to record electrocardiograms and non invasive blood 10 units compared with 5 units. Interventions to prevent pressure and heart rate (HR) was monitored. A blood sample was hypotension during caesarean section may reduce the occurrence obtained 12-hour postoperatively. of ST depressions on electrocardiograms. Main outcome measures Depression of the ST segment. Keywords Caesarean section, electrocardiography, heart, Secondary outcomes: symptoms, Troponon I levels, mean arterial hypotension, ischaemia, oxytocin, regional anaesthesia. pressure (MAP), HR and blood loss. Please cite this paper as: Jonsson M, Hanson U, Lidell C, Norde´n-Lindeberg S. ST depression at caesarean section and the relation to oxytocin dose. A randomised controlled trial. BJOG 2010;117:76–83. 10 Introduction described following oxytocin administration. Systemic haemodynamic changes and/or coronary vasospasm may Electrocardiogram (ECG) changes, suggestive of myocardial impair the myocardial oxygen supply sufficiently to induce ischaemia, have been observed in healthy women during ischaemia, which could be an explanation for the ECG elective caesarean section under regional anaesthesia and changes.5,11 the incidence reported varies from 25% to 60%.1–4 An The value of routine oxytocics in the third stage of caesar- association with oxytocin administration has recently been ean delivery to prevent excessive bleeding has been well estab- described in a randomised trial using 10 units of oxytocin.5 lished and routine oxytocics are also recommended in Oxytocin, given as an intravenous bolus, causes transient patients with cardiac disease.12–14 Doses of oxytocin, as well hypotension, a reflex tachycardia and an increase in cardiac as route of administration, vary widely in clinical practice and output, in healthy women undergoing caesarean section many clinicians are not aware of all the adverse effects of oxy- under spinal anaesthesia.6–8 The magnitude of these effects tocin.15,16 Oxytocin could be detrimental to women who are is dose-related.6,9 Coronary vaso-constriction has also been hypovolemic and to women with cardiac disease.11,15,17–19 76 ª 2009 The Authors Journal compilation ª RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology BJOG. 2010;117(9):1165–6. Cardiac Ischemia 10 IU 5 IU n=103 Br J Anaesth. 2006;98(1):116–9. British Journal of Anaesthesia 98 (1): 116–19 (2007) doi:10.1093/bja/ael302 Advance Access publication December 2, 2006 Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing Caesarean section J. S. Thomas,*, S. H. Koh and G. M. Cooper Department of Anaesthesia, Birmingham Women’s Hospital, Metchley Park Road, Edgbaston, Birmingham B15 2TG, UK *Corresponding author: Department of Anaesthesia, Worcestershire Royal Hospital, Charles Hastings Way, Worcester WR5 1DD, UK. E-mail: [email protected] Downloaded from Background. The cardiovascular effects of oxytocin in animal models and women undergoing Caesarean section include tachycardia, hypotension and decrease in cardiac output. These can be sufficient to5 cause IU significant over compromise 5 minutes in high-risk patients. We aimed to find a simple way to decrease these risks whilst retaining the benefits of oxytocin in decreasing bleeding after delivery. Method. We5 recruitedIU