HHE Sponsored supplement: Managing perioperative bleed - Page 18

PPH evolution, anaemia, need for transfusion and invasive procedures, and maternal morbi- mortality: Hb drop compared with the reference level, percentage of patients developing anaemia (Hb < 8g/dl), requirement for PRBC transfusion or any other blood products, requirement of intrauterine balloon tamponade and/or invasive procedure (arterial ligature, or embolisation, or hysterectomy), and calculated blood loss. Regarding the population selection, evidence has shown that fibrinogen supplementation may be more efficient in patients with hypofibrinogenemia. The study population may therefore be better selected among patients with quite severe PPH at risk of developing coagulopathy. The criteria of selection was to enrol patients at the beginning of prostaglandin (sulprostone; Nalador ® ) administration, which is a time-validated second step of uterotonic treatment in the algorithm of the French PPH management guidelines (30 French guidelines). Prostaglandins are advocated after no more than 30 minutes of ongoing PPH and oxytocin failure. This inclusion criterion has been used previously. 4 Randomisation stratification by centres should protect against the bias of variable team reactivity times in taking the decision for oxytocin– prostaglandin switch. Thromboelastometric identification of coagulopathic patients was not chosen in the FIDEL protocol because most of the centres are not equipped to perform this. References 11 Hogan MC et al. Maternal mortality for 181 countries, 1980-2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet 2010;375(9726):1609–23. 2 Knight M et al. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth 2009;9:55. 3 Abdul-Kadir R et al. Evaluation and management of postpartum hemorrhage: consensus from an international expert panel. Transfusion 2014;54:1756–68. 4 Charbit B et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007;5:266–73. 5 Ducloy-Bouthors AS et al. Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial. Br J Anaesth 2016;116:641–8. 6 Ducloy-Bouthors AS et al. Medical advances in the treatment of postpartum hemorrhage. Anesth Analg 2014;119:1140–7; erratum in 2015;120:494. 7 Sawamura A et al. concentrate (4–8g) might be necessary. In a study by Kikuchi et al, 1g fibrinogen concentrate increased the plasma fibrinogen level to approximately 400mg/l only. 24 Makino et al obtained a similar increase of 32mg/dl/g fibrinogen concentrate administered, which was not sufficient to properly correct severe hypofibrinogenemia in deep coagulopathic atonic patients. 25 The FIDEL trial aims to determine the more efficient place of a 3g dose of fibrinogen concentrate infusion, likely by administering it earlier in coagulopathic patients before PPH becomes life- threatening. This dose was selected on the basis of an anticipated amount of blood loss and corresponding fibrinogen loss at the time of prostaglandin administration. Because the main objective of the study is to assess the benefit associated with an early administration of fibrinogen as a therapeutic strategy, the 3g dose required in the protocol is lower than the 4–8g dose recommended in the Summary of Product Characteristics to treat the most severe PPH. Additional open-label administrations of fibrinogen concentrate will be allowed in both groups, as a rescue therapy, if the severity of the clinical situation requires it, and as per investigator discretion. Which fibrinogen concentrate dose to stop bleeding? The fibrinogen dose administered depends on the severity of haemorrhage as well as on the initial plasma level. Grottke demonstrated that a single dose of 2g and a target level of 1.5g/l was able to avoid death in an experimental design of liver injury in pigs. 9 In cases of severe acute obstetrical haemorrhage, larger doses of fibrinogen Conclusions PPH remains the main cause of maternal death worldwide. An early correction of the PPH- associated coagulopathy process may contribute to a quicker and more efficient bleeding cessation. Because hypofibrinogenemia is a major and early part of PPH-associated coagulopathy, fibrinogen supplementation appears to be one of the most promising targets for this haemostatic intervention. Although recent trials seem to be negative, they have mostly recruited a non- coagulopathic population. The results of the FIDEL trial are awaited. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res 2009;124:608–13. 8 Zacharowski K, Spahn DR. Patient blood management equals patient safety. Best Pract Res Clin Anaesthesiol 2016;30:159–69. 9 Grottke O et al. Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury. Crit Care 2010;14:R62. 10 Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost 2003;29:125–30. 11 Cortet M et al. Association between fibrinogen level and severity of postpartum haemorrhage: secondary analysis of a prospective trial. Br J Anaesth 2012;108:984–9. 12 de Lloyd L et al. Standard haemostatic tests following major obstetric haemorrhage. Int J Obstet Anesth 2011;20:135– 41. 13 Gayat E et al. Predictive factors of advanced interventional procedures in a multicentre severe postpartum haemorrhage study. Intensive Care Med 2011;37:1816–25. 14 Nagashima A. Serum Care 2011;15:R117. 21 WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 2017;389:2105–16. 22 Bell SF et al. The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage. Int J Obstet Anesth 2010;9:218–23. 23 Ahmed S et al. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage – an observational study. Transfus Med 2012;22:344–9. 24 Kikuchi M et al. Fibrinogen concentrate substitution therapy for obstetric hemorrhage complicated by coagulopathy. J Obstet Gynaecol Res 2013;39:770–6. 25 Makino S et al. National survey of fibrinogen concentrate usage for post-partum hemorrhage in Japan: Investigated by the Perinatology Committee, Japan Society of Obstetrics and Gynecology. J Obstet Gynaecol Res 2015;41:1155–60. 26 Mallaiah S et al. Introduction of an algorithm fibrinogen levels could be an index of successful use of balloon tamponade in postpartum hemorrhage. J Perinat Med 2017; DOI 10.1515/ jpm-2016-0238. 15 Huissoud C et al. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. BJOG 2009;116:1097–102. 16 Karlsson O, Jeppsson A, Hellgren M. Major obstetric haemorrhage: monitoring with thromboelastography, laboratory analyses or both? Int J Obstet Anesth 2014;23:10–17. 17 Collins PW et al. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood 2014;124:1727–36. 18 Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014;54:1389–405; quiz 1388. 19 Onwuemene O, Green D, Keith L. Postpartum hemorrhage management in 2012: predicting the future. Int J Gynaecol Obstet 2012;119:3–5. 20 Ducloy-Bouthors AS et al. High-dose tranexamic acid reduces blood loss in postpartum haemorrhage. Crit 18 HHE 2018 | hospitalhealthcare.com for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia 2015;70:166–75. 27 Wikkelso AJ et al. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth 2015;114:623–33. 28 Aawar N et al. Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomized controlled trial. Trials 2015;16:169. 29 Collins PW et al. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. Br J Anaesth 2017;119:411–21. 30 Ducloy-Bouthors AS et al. Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial. Anaesth Crit Care Pain Med 2016;35:293–8. 31 Sentilhes L et al. [Postpartum hemorrhage: Guidelines for clinical practice – Text of the Guidelines (short text)]. J Gynecol Obstet Biol Reprod (Paris) 2014;43:1170–9.