Active Management of Third Stage of Labor 4/15/2017 Active Management of Third Stage of Labor A model to an Evidence Based Obstetric Practice This presentation will: - Briefly review the two methods of third stage management, and present the advantages/disadvantages for each method. - Briefly review the procedure of active management - Present the evidence comparing Active vs. Physiologic Management. - Present available evidence comparing Controlled Cord Traction vs Minimal Intervention. - Present available evidence regarding specific Oxytocic Drugs. - Discuss the available evidence evaluating Nipple Stimulation and effect on PPH. - The latest evidence on new oxytocics.

Active Management of Third Stage of Labor 4/15/2017 Session Objectives To review: Why do we need the introduction of EBM and Information mastery in our day to day practice Definition of third stage of labor Physiologic vs. active management Risks and benefits of each method of management Drugs used in active management Where lies the EVIDENCE Active Management of Third Stage of Labor

Active Management of Third Stage of Labor Half a century ago… “ My students are dismayed when I say to them that half of what they are taught as medical students will in 10 years be shown to be wrong. And, the trouble is,none of their teachers knows which half” Prof. Sydney Burwell Dean of Harvard Medical school Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 Active Management of Third Stage of Labor

Would you care finding your way through the information maze…?! Active Management of Third Stage of Labor

Intermediate Outcomes 4/15/2017 “The Winds of Change” Anecdotes Intermediate Outcomes Negative social and cultural attitudes about family planning and reproductive health, or misunderstandings about them, can also impede access to quality services. Examples of such attitudes include: Females should remain virgins until married, but males should experiment and “test” their sexuality/virility and have multiple partners. Married females should have children before they use contraception in order to prove their fertility. Gender-based violence (including female genital cutting) should be accepted. Family members (e.g., in-laws) should be involved in decision making. Use of contraception or provision of sexuality education will promote promiscuity. Men and boys do not need to have FP/RH services. Youth do not need special FP/RH services (e.g., clinic location, hours, cost, etc. do not need to accommodate youth). Positive social norms, replacing outdated norms, can be created through behavior change and communication and through promotion of a positive image of family planning and contraception. Active Management of Third Stage of Labor

The Pyramid of Evidence 4/15/2017 The Pyramid of Evidence Active Management of Third Stage of Labor

Active Management of Third Stage of Labor Definitions… Clinical guidelines are: ‘Systematically developed statements which assist clinicians and patients in making decisions about appropriate treatment for specific conditions’ Developed using a standardized methodology Active Management of Third Stage of Labor

Active Management of Third Stage of Labor Classification of Evidence Levels - Ia Evidence obtained from meta-analysis of randomized controlled trials. - Ib Evidence obtained from at least one randomized controlled trial. 1 -Ila Evidence obtained from at least one well- designed controlled study without randomization. -Ilb Evidence obtained from at least one other type of well-designed quasi- experimental 2 Evidence obtained from well-designed non- experimental descriptive studies, such as comparative studies, correlation studies . 3 Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities 4 Active Management of Third Stage of Labor

Active Management of Third Stage of Labor Forms of Care… Beneficial Forms of care. Forms of care likely to be beneficial. Forms of care with a trade off. Forms of care with unknown effectiveness. Forms of care likely to be ineffective. Forms of care likely to be harmful. Active Management of Third Stage of Labor

Grades of Recommendation At least one controlled trial Level Ia, Ib B Requires the availability of well controlled clinical studies but no randomised clinical trials on the topic of recommendations. IIa, IIb, III C Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality IV Active Management of Third Stage of Labor

Active Management of Third Stage of Labor To put it short… We need to learn not only to read the medical literature, BUT what to read? And how ? We need to be introduced to the concept of “Information Mastery”. Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 The 5 EBM Skills 1. Forming answerable clinical questions 2. Searching for the best evidence answer 3. Appraising evidence for relevance, impact, validity 4. Integrating the evidence into practice 5. Evaluating & improving Active Management of Third Stage of Labor

A three-part Clinical Question Does active management of the third stage of labor decrease the rate of primary postpartum hemorrhage? The Prevention of Postpartum hemorrhage is by the proper conduction of the third stage of labor This is also a POEM. Active Management of Third Stage of Labor

Where Are You Going To Search For The Evidence…? Textbooks…? Original publications…? Predigested Material Active Management of Third Stage of Labor

Two Methods of Third Stage Management 4/15/2017 Two Methods of Third Stage Management Physiologic (“expectant”) management Oxytocics are not used Placenta is delivered by gravity and maternal effort Cord is clamped after delivery of the placenta Active Management Oxytocic is given Cord is clamped Placenta delivered by controlled cord traction (CCT) with counter-traction on the fundus Fundal massage Active Management of Third Stage of Labor

Critical Issues Pertaining to the Third Stage of Labor 4/15/2017 Critical Issues Pertaining to the Third Stage of Labor Active vs. physiologic management Theoretical potential risks of each Entrapment of placenta Avulsion of cord Uterine inversion Choice of oxytocic agent Stability, safety and side effects of oxytocics Unproven benefit of nipple stimulation CCT and fundal massage if no oxytocic available Active Management of Third Stage of Labor

Physiologic Management: Advantages and Disadvantages 4/15/2017 Physiologic Management: Advantages and Disadvantages Advantages Does not interfere with normal labor process Does not require special drugs/supplies Disadvantages Increases length of third stage Increases risk of postpartum hemorrhage (PPH) Active Management of Third Stage of Labor

Active Management: Advantages and Disadvantages 4/15/2017 Active Management: Advantages and Disadvantages Advantages Decreases length of third stage Decreases risk of PPH Disadvantages Requires oxytocics and items needed for injection Requires a birth attendant with skills in: Observation Giving an injection CCT Active management reduces the duration of the third stage and reduces postpartum hemorrhage. Active Management of Third Stage of Labor

Procedure for Active Management 4/15/2017 Procedure for Active Management Oxytocin Within 1 minute of birth, palpate abdomen to rule out presence of another baby Give oxytocin CCT Await strong uterine contraction (2–3 minutes) Apply controlled cord traction while applying countertraction above pubic bone If placenta does not descend, stop traction and await next contraction WHO recommends giving oxytocin within 2 minutes to give provider time to give injection Continuous gentle traction Uterine massage every 15 minutes for 2 hours Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 Active vs. Physiologic Management: The Bristol and Hinchingbrooke Trials Bristol trial: 1695 women, Hinchingbrooke trial: 1512 women randomly assigned to: Active management Physiologic management Prendiville et al 1988; Rogers et al 1998. Active Management of Third Stage of Labor

Active vs. Physiologic Management: The Bristol Trial Objective 4/15/2017 Active vs. Physiologic Management: The Bristol Trial Objective Compare effects of fetal and maternal morbidity of: Routine active management Physiologic management Prendiville et al 1988. Active Management of Third Stage of Labor

The Bristol Trial: Details of Active Management 4/15/2017 The Bristol Trial: Details of Active Management Try to give one ampule of oxytocic (5 units oxytocin and 0.5 mg ergometrine routinely or 10 units synthetic oxytocin if mother has high BP) immediately after delivery of anterior shoulder Try to clamp cord 30 seconds after delivery of baby When uterus has contracted, try to deliver placenta by CCT with protective hand on abdomen helping to shear off placenta and preventing uterine inversion Try not to give any special instructions about posture Prendiville et al 1988. Active Management of Third Stage of Labor

The Bristol Trial: Details of Physiologic Management 4/15/2017 The Bristol Trial: Details of Physiologic Management Try not to give oxytocic Try to leave cord attached to baby until placenta is delivered Try not to use CCT or any manual interference with uterus at fundus Try to encourage mother to concentrate on feeling for next contraction or urge to push When mother feels contraction or urge or there are signs of separation, encourage mother and help her change posture If placenta does not deliver spontaneously, wait, try putting baby to breast and encourage maternal effort Prendiville et al 1988. Active Management of Third Stage of Labor

Active vs. Physiologic Management: Postpartum Hemorrhage 4/15/2017 Active vs. Physiologic Management: Postpartum Hemorrhage Active Management Physiologic Management OR and 95% CI Bristol Trial 50/846 (5.9%) 152/849 (17.9%) 3.13 (2.3-4.2) Hinchingbrooke Trial 51/748 (6.8%) 126/764 (16.5%) 2.42 (1.78-3.3) The rate of postpartum hemorrhage was significantly lower with active management than with physiologic management in both trials (5.9% vs. 17.9% [Bristol] and 6.8% vs. 16.5% [Hinchingbrooke]). Prendiville et al 1988; Rogers et al 1998. Active Management of Third Stage of Labor

Active vs. Physiologic Management: Results 4/15/2017 Active vs. Physiologic Management: Results Active Management Physiologic Management OR and 95% CI Duration 3rd stage (median) Bristol 5 minutes 15 minutes Not done Hinchingbrooke 8 minutes Third stage > 30 minutes 25 (2.9%) 221 (26%) 6.42 (4.9-8.41) 25 (3.3%) 125 (16.4%) 4.9 (3.22-7.43) Blood transfusion 18 (2.1%) 48 (5.6%) 2.56 (1.57-4.19) 4 (0.5%) 20 (2.6%) 4.9 (1.68-14.25) Therapeutic oxytocics 54 (6.4%) 252 (29.7%) 4.83 (3.77-6.18) 24 (3.2%) 161 (21.1%) 6.25 (4.33-9.96) The duration of third stage was reduced, as well as the need for blood transfusion and therapeutic oxytocics in the active management groups compared to the physiologic management group. Active Management of Third Stage of Labor

Active vs. Physiologic Management: The Bristol & Hinchingbrooke Trials 4/15/2017 Active vs. Physiologic Management: The Bristol & Hinchingbrooke Trials Conclusion: Active management of the third stage reduces the risk of PPH: Increased risk of PPH associated with physiologic management Increased need of blood transfusion associated with physiologic management Oxytocin was drug of choice for active management No increase in entrapment of placenta with active management Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 Oxytocic Drugs Oxytocin- posterior pituitary extract Ergometrine- preparation of ergot Syntometrine- combination of oxytocin and ergometrine Misoprostol- prostaglandin E1 analogue Misoprostol holds promise for use as an oxytocic. It is effective, practical and inexpensive. In contrast to the other three oxytocics, misoprostol is stable (heat, light) and does not have to be given by injection. It can be given orally or rectally. Active Management of Third Stage of Labor

Oxytocic Drugs: Oxytocin 4/15/2017 Oxytocic Drugs: Oxytocin Advantages Causes uterus to contract Acts within 2.5 minutes when given IM Generally does not cause side effects Disadvantages More expensive than ergometrine IM or IV preparations only Not heat stable Active Management of Third Stage of Labor

Oxytocic Drugs: Ergometrine 4/15/2017 Advantages Low price Effect lasts 2–4 hours Disadvantages Takes 6–7 minutes to become effective when given IM; oral form insufficiently effective Causes tonic uterine contraction Increased risk of hypertension, vomiting, headache Contraindicated in women with hypertension or heart disease Not heat stable Active Management of Third Stage of Labor

Oxytocic Drugs: Syntometrine 4/15/2017 Oxytocic Drugs: Syntometrine Advantages Combined effect of rapid action of oxytocin and sustained action of ergometrine Disadvantages Increased risk of hypertension, nausea and vomiting Not heat stable Active Management of Third Stage of Labor

Oxytocin vs. Syntometrine: Objective and Design 4/15/2017 Oxytocin vs. Syntometrine: Objective and Design Objective: To compare effects of syntometrine with oxytocin in reducing the risk of PPH and other maternal and neonatal outcomes Design: Randomized controlled trials McDonald, Prendiville and Elbourne 2000. Active Management of Third Stage of Labor

Oxytocin vs. Syntometrine: Results 4/15/2017 Oxytocin vs. Syntometrine: Results Syntometrine was associated with a small reduction in risk of PPH < 1000 mL (OR 0.74, 95% CI 0.65-0.85) Adverse effects of vomiting and hypertension were associated with the use of syntometrine There were no differences in other maternal or neonatal outcomes McDonald, Prendiville and Elbourne 2000. Active Management of Third Stage of Labor

Oxytocin vs. Syntometrine: Conclusion 4/15/2017 Oxytocin vs. Syntometrine: Conclusion Need to weigh benefit of reduction in risk of PPH with risk of other adverse effects associated with syntometrine Because syntometrine has more side effects: nausea, vomiting and increased blood pressure, it is less safe. Therefore, since oxytocin is equally effective and safer, it should be the first choice. McDonald, Prendiville and Elbourne 2000. Active Management of Third Stage of Labor

Stability of Oxytocics in Tropical Climates: Objective and Design 4/15/2017 Stability of Oxytocics in Tropical Climates: Objective and Design Objective: To determine pattern of stability in long term dark storage, short term exposure to high temperature and light To develop guidelines Methods: Tested field samples of ergometrine and methylergometrine and also simulated field storage conditions at different temperature/light exposure WHO 1993. Active Management of Third Stage of Labor

Stability of Oxytocics in Tropical Climates: Results 4/15/2017 Stability of Oxytocics in Tropical Climates: Results Field: Ergometrine: only 31% of samples had compliant level of active ingredient Oxytocin: one expired, 5 samples had 104–142% of stated amount of active ingredient WHO 1993. Active Management of Third Stage of Labor

Stability of Oxytocics in Tropical Climates: Results (continued) 4/15/2017 Stability of Oxytocics in Tropical Climates: Results (continued) Simulation condition Ergometrine/ methylergometrine Oxytocin Refrigeration for 12 months Lost 4-5% active ingredient No loss 30oC, dark Lost 25% Lost 14% 21–25oC, light Lost 21–27% in one month >90% in 12 months Lost 5% 40oC dark Lost > 50% Lost 80% WHO 1993. Active Management of Third Stage of Labor

Stability of Oxytocics in Tropical Climates: Conclusions 4/15/2017 Stability of Oxytocics in Tropical Climates: Conclusions Stability of oxytocin is better than ergometrine/ methylergometrine, especially regarding light Store refrigerated, in dark, labeled Remove from box only for immediate use Short periods unrefrigerated are fine (1 month at 30°C, 2 weeks at 40°C) Oxytocics are not heat stable, but oxytocin is better than ergometrine/methyl-ergometrine. WHO 1993. Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 Nipple Stimulation Nipple stimulation has not been shown to reduce risk of PPH Randomized controlled trial of suckling immediately after birth with over 4,000 subjects in Malawi showed no significant difference in frequency of PPH, mean blood loss or retained placenta When oxytocics are not available, CCT and fundal massage should be performed Advantages of early breastfeeding and nipple stimulation: Stimulates natural production of oxytocin May maintain tone of contracted uterus Benefits baby Need oxytocics; efforts should be made to make it available at all levels of care. Getting the uterus to contract probably requires some “surge” of oxytocin, such as that delivered by an injection of oxytocin. When oxytocics are not available, CCT and fundal massage should be performed. Natural oxytocin produced by suckling of baby at breast may be useful for helping to maintain the tone of an already contracted uterus. Bullough, Msuku and Karonde 1989. Active Management of Third Stage of Labor

Recommendations Concerning Selection of Oxytocic 4/15/2017 Recommendations Concerning Selection of Oxytocic Use oxytocin, when available: If oxytocin is not available, use syntometrine or ergometrine If oxytocic drugs are not available, use nipple stimulation Remember: Do not use ergometrine in women with hypertension or heart disease Store oxytocics in refrigerator (2–8ºC) and away from light Misoprostol rectally has advantages; awaiting confirmatory studies. Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 Summary Active management of third stage includes: Oxytocin Controlled cord traction Fundal massage Ensuring supply of oxytocin is a priority Active Management Reduces risk of PPH Retained placenta Need for therapeutic oxytocics Need for blood transfusion Active Management of Third Stage of Labor

Active Management of Third Stage of Labor 4/15/2017 References Bamigboye A et al. 1998. Randomized comparison of rectal misoprostol with syntometrine for management of third stage of labor. Acta Obstet Gynecol Scand 77: 178–181. Bullough CH, RS Msuku and I Karonde. 1989. Early suckling and postpartum haemorrhage: Controlled trial in deliveries by traditional birth attendants. Lancet 2(8662): 522–525. Irons DW, P Sriskandabalan and CHW Bullough. 1994. A simple alternative to parenteral oxytocics for the third stage of labor. Int J Obstet Gynecol 46:15–18. Khan GQ et al. 1997. Controlled cord traction versus minimal intervention technique in delivery of the placenta: A randomized controlled trial. Am J Obstet Gynecol 177(4): 770–774. Active Management of Third Stage of Labor

References (continued) 4/15/2017 References (continued) McDonald S, W Prendiville and D Elbourne. 2000. Prophylactic syntometrine versus oxytocin for delivery of the placenta (Cochrane Review), in The Cochrane Library. Issue 4. Update Software: Oxford. McDonald et al. 1993. Randomized controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labor. BMJ 307(6913):1167–1171. Prendiville et al. 1988. The Bristol third stage trial: active versus physiological management of the third stage of labor. BMJ 297:1295–1300. Rogers J et al. 1998. Active versus expectant management of third stage of labour: The Hinchingbrooke randomised controlled trial. Lancet 351(9104): 693–699. World Health Organization (WHO). 1993. Stability of injectable oxytocics in tropical climates: Results of field surveys and simulation studies on ergometrine, methylergometrine, and oxytocin. WHO: Geneva. Active Management of Third Stage of Labor