Strengths and Limitations
To our best knowledge, this was the first study to develop initial fluid treatment with HbV infusion for severe PPH. The resuscitative benefit of HbV treatment in the initial hours led to maintenance of normal lactate levels that in turn resulted in adequate oxygen supply. This indicates that prompt HbV infusion might help stabilise the haemodynamics and enable transport to secondary or tertiary facilities.
Our findings should be interpreted with caution in the context of the principal limitations of the current study. First, the efficacy of HbVs for severe PPH was evaluated in an animal model, and thus the applicability of the findings in humans need to be further verified. Second, this study did not investigate the long-term safety of HbVs beyond the acute setting. Third, we did not precisely investigate the effects of HbVs on the foetus, including intrauterine resuscitation in this study. A previous study reported the efficacy of HbVs for chronic placental hypoxia and improvement of foetal growth restriction in a rat pre-eclampsia model36. However, there are no reports on the efficacy of intrauterine resuscitation of foetuses for low uteroplacental blood flow due to acute massive peripartum haemorrhage, including placental abruption. In this study, the HbV group showed dilutional coagulopathy due to lack of coagulation factors. Methods for controlling coagulopathy using other blood substitutes with haemostatic capacity, including PLT substitutes,23 should be further investigated.
Furthermore, this study had methodological limitations. Measurement of systemic NOx levels did not always reflect NO metabolism at the cellular levels. Further studies are needed to validate our findings and ultimately establish the use of HbVs for severe PPH in clinical practice.