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For each woman who dies during pregnancy, 30 women suffer complications. Initiatives should include: Family planning Management of complications of abortion Management of complications of pregnancy and childbirth
From Evolution to ancient oxytocics 3.5 thousand years ago, Egyptians were fully aware of the current problem: If you could promote uterine contraction, you would speed labour and stem haemorrhage. Papyrus Ebers recommends various recipes, like… … Fly excrement is even mentioned in various ancient pharmacopoeias. 100 AD Discorides a Greek physician lived at Nero’s time recommends cyclamen, a flower. 1600 anno domini, Gerad a British herbalist advices chervil, a pot herb. This all has nothing to do with an OT agonist, I do not know, if it works, but it concerns exactly the same life threading indication! Finally ergot came up, extracts and alkaloids from a fungus on rye. Longer used than OT, it causes strong uterine contraction, abortions, but is more toxic: nausea, vomiting, and hypertension
About 60 years ago, OXT was synthesised by Vincent du Vigneaud, an American biochemist. Driven by his interest in sulphur containing amino acids he managed to isolate OXT and ADH from crude pituitary preparations. He identified the structure of the nona-peptide. Here a chromatogram shows separated amino acids of the hydrolysate and an identical chromatogram from a mixture of artificial amino acids. He succeeded with the synthesis of the first polypeptide hormone, put the amino acids together in the right sequence, closed the ring and finally proved chemical properties and physiological activity. The most thrilling experience: The synthetic polypeptide and the natural product were identical. At that time, it wasn’t taken for granted that synthetic and natural products behave chemically and pharmacologically identical.
Today, OT alone or in combination with ergometrin is globally available. However there are regional differences regarding the recommended use. The slide is not complete and does not mean OT is always the treatment of choice. It is described in monographs of several pharmacopoeias such as… Most known brands are Syntocinon from Novartis, Pitocin from Pfizer etc. However some of the products have been withdrawn form the markets. There are two major indications: OT infusions are useful to induce and augment labour. For PPH it is used alone or in combination with ergometrin. And there are additional indications such as: OT injected in umbilical cord vein to assist removal of a retained placenta. In the past, as nasal spray with good BA was used, it can induce lactation. OT challenge test to detect placental insufficiency and still birth risk: OT is infused in third trimester and the baby is monitored for heart rate anomalies. Finally in abortion it plays probably more a theoretical than practical role.
The next slide is dedicated to OT agonists. Carbetocin it is a long-acting synthetic analogue of OT. It contains a thioether instead a disulfide bridge, it lacks an amino acid - cysteine 1, and a phenol alcohol is blocked by a methyl ether. It is used for treatment of uterine atony following Caesarean section and in veterinary medicine. To my knowledge this is the only therapeutically or commercially relevant oxytocin agonist. An incredible number of OT derivatives have been synthesized, from different companies, from universities, from professors Manning +others some are published/patented, but I am not aware that any of them reached great relevance so far. However, there are some experimental peptides published like hydroxy threonine OT And more recently there is again activity in non-peptide, central agonists such as the following: There is a series of compounds patented for erectile dysfunction and from Wyeth-Ayerst a series for treatment of anxiety and schizophrenia-related diseases. Another series including compound 39 from ex-Ferring UK.
molto bassa-debole .E sottolinea i potenziali effetti dannosi
Nell’immagine in 3D si evidenzia la perfetta aderenza tra bakri e parete uterina
Efecto: transfomra la circulación pélvica en un sistema venoso Criterio de selección Hemodinámicamente estables Preservar fertilidad Experiencia del cirujano Éxito en el 42% de los casos (Clark, 1985)
Ribaltare il problema: non più la donna in radiologia,bensì il radiologo in sala operatoria,se adeguata programmazione sanitaria (sale operatorie schermate,lettino operatorio radiotrasparente,angiografo portatile.Non necessariamente Maometto che va alla montagna,ma è anche possibile che la montagna vada da Mometto
Quando la muscolatura uterina perde la capacità contrattile va in atonia e pertanto il tamponamento uterino può non essere sufficiente ad evitare la miopatia dilatativa.Con le bretelle della B-Lynch contropressione e quindi compressione sia estrinseca che intrinseca
Indispensabili sala schermata;angiografo portatile;lettino operatorio radiotrasparente.Preferibile l’approccio transomerale in quanto permette ,in caso di bisogno, alle due equipe di lavorare contemporaneamente;Il team di sala indossa grembiule piombato
Con angiostati ,pinze di Satinski o pinze ad anelli.Abbiamo aggiunto questo step da febbraio (placenta percreta).Da allora uso sistematico in quanto riduce in maniera significatica l’entità della “ marea montante”.Abbiamo iniziato con gli angiostati che però sono pinze estremamente delicate che sono ottimali per clampaggio diretto dei vasi,meno efficaci quando devono comprendere tessuto interposto.Attualmente Satinski
A destra suture quadrate poste sulla parete posteriore; a sinistra sulla parete aanteriore (bisogna preventivamente scollare la vescica ed evitare di trapassare all’esterno.
60mm ;1/2 circonferenza
Nelle immagini ,a scopo didattico,tutte le operazioni sono eseguite ad utero esteriorizzato:Se non vi è sufficiente spazio riposizionare l’utero nella pelvi e poi procedere con isterorrafia,gonfiaggio,legatura della B-Lynch. Molta attenzione nel non bucare accidentalmete il pallone durante l’isterorrafia o durante l’apposizione di punti emostatici aggiuntivi
Nei piccoli sanguinamenti a nappo,specie in precarie condizioni coagulative.In passato molto impiegato il FloSeal,oggi ritenuto più maneggevole il Quixil (possibilità anche di erogazione con nebulizzatore.Costo inferiore)
Estremamente importante il separatore cellulare che ci permette di processare parte del sangue perso e recuperarlo;fondamentale nell’immediato postoperatorio recuperare e mantenere una adeguata temperatura corporea.
Potremmo essere accusati di “over treatment”,e di eccessivo utilizzo di risorse.Almeno in interventi di elezione,in casi già noti ad alto rischio emorragico bisogna predisporre la massima messa in sicurezza possibile,per ridurre al minimo il rischio materno.
Placenta previa centrale:notevoli lacune Vascolari che infiltrano il miometrio.Non ben evidenziabile il tessuto miometrale da quello placentare.deformazione dell’impronta vescicale.riscontro al color doppler e in basso alla elaborazione 3D dei vasi
Dall’alto scansione sagittale 17 e scansione sagittale 13 con soppressione grasso (Fat Suppression) In basso scansioni coronali 9 e 11
A nostro avviso risultato impensabile senza l’impiego delle risorse utilizzate.Quanti avrebbero salvato l’utero?
MANAGEMENT OF POST-PARTUM HEMORRHAGEGC DI RENZO, MD, PHD, FRCOG, FACOGPERUGIA, ITALY
Why focus on preventing post-partum hemorrhage? Haemorrhage is the largest direct cause of maternal death PPH is mostly unpredictable Most PPH is caused by uterine atony Evidence-based, feasible, low-cost interventions exist Active management at the third stage of labour can prevent 60% of PPH
Difficulties associated with comparing post-partum hemorrhage studies Method to determine blood loss – Visual underestimation 70–80% Conduct during third stage of labour Confounding factors in epidemiological studies 58% of trials do not report their definition of PPH
Maternal Health: some ( underestimated) statistics 180–200 millions pregnancies per year 75 millions unwanted pregnancies 50 millions induced abortions 20 millions unsafe abortions 358,000 maternal deaths (1000 per day) 1 death every 1,5 min 20 maternal morbidities per minute 10-15 millions disabilities each year WHO, 2010
Maternal Death Clock 380 women become pregnantEvery Minute... 190 women face unplanned or unwanted pregnancy 110 women experience a pregnancy related complication 40 women have an unsafe abortion 1 woman dies from a pregnancy- related complication 20 women suffer of a disabilty related to childbirth WHO, 2010
About two thirds of maternal deaths are due to Anemia-Hemorrhage Obstructed delivery They can be Eclampsia treated by a health Sepsis professional Unsafe abortion
Maternal mortality from post- partum hemorrhage in the UK 6 Maternal mortality rate/million 5 4 3 2 1 0 85–87 88–90 91–93 94–96 97–99 00–02 YearHall M. 2004; Why mothers die (2000–2002) CEMACH. 88% received substandard care
Sub-standard care Organisational problems – Inappropriate booking – Inadequate blood transfusion – Intensive care facilities Poor quality of resuscitation – Inadequate transfusion – Blood products Equipment failure – Malfunctioning of specimen transport system Failure to recognise or treat antenatal medical conditions – Inherited bleeding disorders Failure of senior staff to attendHall M. 2004; Why mothers die (2000–2002) CEMACH. Concerns about the quality of surgical treatment
As with many problems, there seems to be two different kinds of emergencies... ...depending on whether the patient is in a developed or undeveloped country
Post-partum hemorrhageEqual opportunity Not equal occurrence opportunity killer 2/3 no risk factors Poor Malnourished Unhealthy
What is post-partum hemorrhage? Excess blood loss after the birth of a baby PPH >500 ml (3.5– 30%) Severe PPH >1000 ml (1.5–5.0%) Immediate PPH: – Onset within 24 h of birthThese definitions are notPPH late: accepted by all!! – Onset after 24 h of birth
One of the main problem……UNDERESTIMATION OF BLOOD LOSS
Methods used to diagnose post-partum hemorrhage Clinical methods – Physiological response to blood loss Quantitative methods – Visual assessment – Direct collection of blood into bedpan or plastic bags – Gravimetric method – Changes in hematocrit and haemoglobin – Others Plasma volume Tagged erythrocytes
Estimated blood loss 30 Visual Measured Estimated blood loss (%) 25 20 15 10 5 0 >500 ml >1,000 mlPrasertcharoensuk et al. IJGO 2000
Risk factors1. placenta previa with or without previous uterine surgery.2. previous myomectomy.3. previous cesarean delivery.4. Ashermans syndrome. (treated surgically)5. submucous leiomyomata.6. maternal age of 36 years and older.
Risk factors (multivariable analysis) Retained placenta, OR=3.5 Failure to progress to second stage, OR=3.4 Placenta accreta, OR=3.3 Lacerations, OR=2.4 Instrumental delivery, OR=2.3 Newborn large for gestational age, OR=1.9 Hypertensive disorders, OR=1.7 Induction of labour, OR=1.4 Augmentation of labour with oxytocin, OR=1.4Sheiner E, et al. J Matern Fetal Neonatal Med 2005.
Obstetrics & Gynecology 1985;66:89-92Placenta Previa/Accreta and Prior Cesarean SectionSTEVEN L. CLARK Et al The risk of placenta previa was 0.26% with an unscarred uterus and increased almost linearly with the number of prior cesarean sections to 10% in patients with four or more. With a placenta previa and one previous cesarean section, the risk of placenta accreta was 24%; this risk continued to increase to 67% (two of three) with a placenta previa and four or more cesarean sections.
Joint statement management of the third stage of labour to prevent post-partum hemorrhage Active management of the third stage of labour should be offered to women since it reduces the incidence of post-partum haemorrhage due to uterine atony – Consists of interventions designed to facilitate the delivery of the placenta by increasing uterine contractions and to prevent PPH by averting uterine atony. The usual components include: Administration of uterotonic agents Controlled cord traction Uterine massage after delivery of the placenta, as appropriate Every attendant at birth needs to have the knowledge, skills and critical judgment needed to carry out active management of the third stage of labour and access to needed supplies and equipment
Maternal outcomes of active management trials Active management 30 Physiological management Patients (%) 20 10 0 Transfusion Prolonged Therapeutic Low Retained third stage uterotonic haemoglobin placenta drugsMcCormick et al, IJGO 2002
POSTPARTUM HEMORRHAGE need of “ action” in the “golden hour” in order to increase the probability of patient survival:The mnemonic HAEMOSTASIS can assist in rememberingthe sequence of events to confront
HAEMOSTASISA: evaluate the vital parameters of the patient and the amount of bloodloss
HAEMOSTASISE: identify the cause (ethiology) and the appropriatetreatment (4T) Tone Tissue Trauma Trombin
Causes of post-partum hemorrhage (4T) TONE (70%) TRAUMA CAUSE TISSUE (19%) (10%) THROMBIN (1%)Anderson et al. Am Fam Physician 2007.
RISK FACTORS Etiology Process Clinical Risk Factors Tone Overdistended Uterus Polyhydramnios, Multiple Gestation Macrosomia Uterine Muscle Fatigue Rapid Labor, Prolonged Labor High Parity Intra Amniotic Infection Fever, Prolonged ROM Functional/Anatomic Distortion of the Fibroid Uterus Uterus Placenta Previa Uterine Anomalies Tissue Retained Products Incomplete Placenta at Delivery Abnormal Placenta Previous Uterine Scar High Parity Retained Blood Clots Atonic UterusTrauma Lacerations Precipitous or Operative Delivery Extensions at C/S Malposition, Deep Engagement Uterine Rupture Previous Uterine Surgery Uterine Inversion High Parity, Fundal PlacentaThrombin Pre-existing Coagulopaties, Liver Disease Acquired in Pregnancy ITP, DIC Therapeutic Anti-coag History of DVT or PE
HAEMOSTASISO: proceed with oxytocin infusion, prostaglandins ( via rectal, intramuscolar, IV, intramyometrial) First line Second line Third line (off label)
Drugs to prevent and treat uterine atony•Prophylactic syntometrine versus oxytocin•Prophylactic use of oxytocin•Carbetocin•Injectable prostaglandins•Misoprostol
Ancient Oxytocics• Egyptian Papyrus Ebers, 1500 BC contract uterus: speed birth, stem haemorrhage hemp in honey celery in milk juniper berries fly excrement (in many ancient pharmacopoeias)• Dioscorides: cyclamen, 100 AD• Ergot (Claviceps purpurea), 1582 AD 40
1953: Synthesis of Oxytocin Vincent du Vigneaud – American biochemist – discovery, isolation, and synthesis together with ADH/vasopressin• Nobel prize in chemistry 1955 sulphur compounds of high importance first synthesis of a polypeptide hormone The Nobel Foundation 1955 http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/oxytocin.gif T Reinheimer, 2009 41
Oxytocin Today – oxytocin (sometimes combined with ergometrin)• Labour induction/augmentation• Prophylaxis and Treatment of Postpartum haemorrhage retained placenta: umbilical vein injection milk ejection/lactation: oxytocin nasal spray Martindale 2008 http://www.appdrugs.com/ProdJPGs/OxytocinLg.jpg T Reinheimer, 2009 42
Oxytocin Agonists Carbetocin (DURATOCIN, PABAL) – long-acting synthetic analogue – indication: prevention of uterine atony – veterinary medicine• Non-peptide agonists patented for erectile dysfunction WAY-262464: patented for anxiety, schizophrenia Pritt et al. 2004, Manning et al. 2008 http://www.bcnpeptides.com/images/products/carbetocina.jpg WO/2003/000692, US/20070117794 T Reinheimer, 2009 43
Mean arterial pressure (MAP) changes with oxytocin • 30 women with elective Mean change of MAP (mmHg) caesarean section • 5 u of oxytocin either as a bolus injection or an infusion over 5 min • Heart rate and intra- arterial blood pressure recorded every 5 s Study period (s)Thomas JS, et al. Br J Anaesth 2007
N=240Study design: Prospective double-blind randomized controlled studyDrugs: Carbetocin 100 µg i.m. vs. syntometrine (5 IU of oxytocin and0.5 mg of ergometrine) i.m.Primary outcome: postpartum hemorrhage requiring additional uterotonictherapySecondary outcome: incidences of postpartum hemorrhage (>500 ml) and severepostpartum hemorrhage (>1,000 ml) as well as adverse effects profile
Authors Conclusion:A single dose of intramuscular carbetocin 100µg may be more effective as compared to a single intramuscular dose of syntometrine (5 IU of oxytocin and 0.5 mg of ergometrine) in reducing postpartum blood loss Lower incidence of adverse effects.
N=377Study design: double-blind randomised single centre studyDrugs: carbetocin 100 µg or oxytocin 5 IU, both i.v.Primary outcome: Need of additional pharmacological oxytocic interventions.Secondary outcomes: Estimated blood loss, difference in preoperative andpostoperative haemoglobin, incidence of blood transfusion and adverse effects
Authors conclusion:Carbetocin reduces the use ofadditional oxytocics followingcaesarean section when compared withthe licensed dose of oxytocin (5 IU)
Carbetocin versus oxytocin • REVIEW: Oxytocin agonists for preventing PPH • COMPARISON: 01 Carbetocin versus oxytocin • OUTCOME: 02 Use of additional uterotonic therapy Carbetocin Oxytocin RR (Fixed) Weight RR (Fixed) Study n/N n/N 95% CI (%) 95% CI 01 Caesarean delivery Boucher 1998 0/29 3/28 100 0.14 (0.01, 2.56) Dansereau 1999 15/317 32/318 900 0.47 (0.26, 0.85) Subtotal (95% CI) 346 346 100.0 0.44 (0.25, 0.78) Total events: 15 (carbetocin), 35 (oxytocin) Test for heterogeneity chi-square=0.66; df=1; p=0.42; I 2=0.0% Test for overall effect z=2.81; p=0.005 02 Vaginal delivery Boucher 2004 12/83 12/77 100.0 0.93 (0.44, 1.94) Subtotal (95% CI) 83 77 100.0 0.93 (0.44, 1.94) Total events: 12 (carbetocin), 12 (oxytocin)Su LL, et for Cochrane Database Syst Rev. 2007 Test al. heterogeneity not applicable 0.001 0.1 1 10 100 1000 Favours carbetocin Favours oxytocinJul Test for overall effect z=0.20; p=0.8 18;(3):CD005457
ConclusionsPrevention of PPHVaginal birth: active management, Oxytocin (3-5 IU), noprostaglandins, no ergometrinCaesarean section: Carbetocin (Pabal®), Oxytocin 5IU 2-3min –no bolus, no PGs, no ergometrinTherapy of PPHOT (10-40 IU/liter), ergometrin (0.2mg every 2-3 hours)PGE2/PGF2alpha (0.25 mg i.m. every 15-90 min)Misoprostol 800-1000mcg rectally (off label)Carbetocin (off label)
HAEMOSTASISS: transfer the patient to the operating room( exclude trauma or retained products, proceed with bimanual compression)
TAMPONADE WITH BAKRI BALLOON– Simple and efficient (87-95 % success rate)– Applicable after cesarean and vaginal births– Used as method of prevention in “cesareans at high hemorrhagic risk” (placental pathologies, uterine over-distension, preeclampsia, precedent hysterotomy, coagulopathy, etc) and in the case of contraindications for prostaglandins (asthma, glaucoma, important hepatic and renal dysfunction)– Easy to insert and remove– Continuous monitoring of blood loss
BAKRI BALLOON The Bakri is a balloon in silicon, latex-free, which is filled with physiological solution (500 cc max) and is able to create a real intrinsic compression on the myometrial walls: the filling volume can be varied in relation to the dimension of the uterus and the contractile response Additionally to the ease of insertion it has the possibility to monitor the amount of blood loss thanks to the drainage holes located in the distal part of the catheter, which is attached to a sac in order to collect the fluids. This access is used also to perform washings of the uterine cavit y. Associate adequate antibiotic coverage Removal of the balloon within 24 hrs administering uterotonics/uterokinetics before deflating
HAEMOSTASIS A: apply “compressive sutures”Hayman uterine compressive sutures Cho multiple quadrate sutures Does not necessitate to open the uterine cavity
HAEMOSTASIS A: perform “ sutures”Suture of Hayman
HAEMOSTASIS S: Systematic pelvic devascularization Rescue Surgery: Ligation uterine artery and ovarian arteryTriple ligation of Tsiruinikov : ligation of the uterine arteries, round ligament and the uterine-ovarian.
Vascular ligation – Uterine – Ovarian – Int iliac
HAEMOSTASIS S : Subtotal or total abdominal hysterectomyRescue Surgery : total hysterectomy / subtotal 1.55 % births 0.24% and 0.90% of all cesarean sectionsISTAT 2006 between 1480 and 1800 hysterectomies/year associated with cesarean section
The ideal treatment should be: intuitive and easy to apply secure and effective in the“prevention” and the arrest of hemorrhages has an immediate result avoids hysterectomy
•TEAM- Obstetricians, Anesthetists,Blood bank, Interventional Radiologists Max therapeutic efforts within 2-3 hrs Contemporary involvement of all professional figures Liberal use of all therapeutic agents
Prevention of postpartum hemorrhage ( cases at elevated hemorrhagic risk:ex. placenta previa in post-C.S. ) Assistance Plan STEP 2 Squared hemostatic endouterine suturesRationale: at the level of the inferior uterine segment reduced muscularcomponent ; incomplete mechanical hemostasis after placental delivery;conspicuous hemorrhage multiple quadrate sutures in the IUS of 2-3 cm, transdecidual. (Dexon n.1- 2,needle with large curvature ) Retraction of the muscular fibers with clamping and e occlusion of the vasculature m s Affront i
Prevention of postpartum hemorrhage( cases at elevated hemorrhagic risk:ex. placenta previa in post-C.S. ) Assistance Plan STEP 3 B-Lynch compressive sutures The ligature of the sutures follows after STEP 4
Considerations All pregnancies are at risk of hemorrage in the post partum even if at the moment of birth there were no risk factors.Because our goal is to improve maternal health and prevent the possibility of death during the pregnancy or birth it is fundamental to possess, other than a solid preparation, a trustworthy and well trained team and the necessary instruments. ( Bakri balloon;Cell sorter with continuous flow; FloSeal)
New conservative approach in the management of PPH G. Clerici, G. Epicoco, E. Bottaccioli, S. Arena, I. Giardina, G. C. Di Renzo, G. Affonti University Hospital of Perugia, Perugia, Italy CONSERVATIVE MANAGEMENT PROTOCOL METHODS A retrospective study of 49 patients (since October STEP 1 –Preliminary prophylactic 2007) with placenta previa/accreta who underwent a catheterization of the descending aorta conservative management protocol (see table). STEP 2 –Extraction of the fetus by C.S. and RESULTS placental delivery E M S Conservative management of PPH was successfully Affronti achieved in 48 patients (98%). In only one case it was STEP 3 –Multiple quadrate endouterine necessary to perform post-partum hysterectomy for haemostatic sutures massive bleeding due to severe placental accretism. In another case it was necessary selective STEP 4-Preparation of B-Lynch compressive embolization of the right uterine artery due to the sutures presence of hematoma in the right part of the lower uterine segment and in the right paracolpus. STEP 5 –Application of hydrostatic balloon The mean estimated blood loss was 1620 ml (range (Bakri balloon) 1100-2340 ml). The mean hospital stay was 5.5 days (range 4-10 days). 22 patients (45%) underwent STEP 6 –Repositioning of uterus - uterineINTRODUCTION sutures - hydrostatic balloon inflation – B- intraoperative and postoperative blood transfusionsPostpartum hemorrhage (PPH) is the leading Lynch ligature and the mean transfused volume was 700 ml. 18cause of maternal death worldwide. Most patients (37%) were admitted for 24-48 h to intensivedeaths occur within the first 4 hours after If the maneuvers fail the next step is care unit for intensive monitoring. 30% of patientsdelivery, often as a consequence of placental devascolarizating ligature/selective experienced moderate fever in the first 24-48 h anddelivery. Treatment option for PPH include embolization of the uterine arteries. they were treated with antibiotics.conservative management (uteritonic drugs, If all procedures fail, proceed withselective devascularization by ligation or hysterectomy.embolization of the uterine artery, external CONCLUSIONScompression with uterine sutures and • Monitoring of maternal hematologic All pregnancies are at risk of PPH. Its management isintrauterine packing). Failure of these parameters 24 hrs before C.S. and 2 h after dictated by several considerations includingoptions necessitates hysterectomy. the procedure, than every 2-4 h for the hemodynamic status and desire to preserve fertility.The objective of the study is to report our following 24 hrs in relation to clinical Conservative interventions should representexperience with a conservative management conditions. mandatory step for treatment of PPH in high riskprotocol to treat PPH in high risk patients • Blood transfusion if the hemoglobin level patients with placenta previa/accreta. The results ofdiagnosed with placenta previa/accreta. decreases more than 7 g/dl and the this conservative protocol are encouraging . hematocrit value is less than 21% ; • The Bakri balloon is removed 24 h after delivery.
FACTS:All pregnancies are at risk ofPPH even if no predisposing factors are presentLuis G. Keith 2007
BOTTOM LINE Averting maternal death is based on having a prepared mind, a prepared team and a full range of possible therapiesLuis G. Keith, 2007
Postpartum HemorrhageRecommendations: •Every department needs to have a protocol for management of O.E., with periodic re-evaluation (Life Support training) •Cases at risk of E.O. need to give birth in a II-III level structure •Uncontrollable hemorrhages may necessitate hysterectomy: an expert surgeon needs to be avaliable quickly 24 hrs a day •Activate the multidisciplinary team early in the management of a case at risk •Institutional guidelines for the treatment of hemorrhages with periodic simulation training (skills and drills)