A Novel Cross-Linked Hemoglobin-Based Oxygen Carrier, YQ23, Extended the Golden Hour for Uncontrolled Hemorrhagic Shock in Rats and Miniature Pigs

Background: Hypotensive resuscitation is widely applied for trauma and war injury to reduce bleeding during damage-control resuscitation, but the treatment time window is limited in order to avoid hypoxia-associated organ injury. Whether a novel hemoglobin-based oxygen carrier (HBOC), YQ23 in this study, could protect organ function, and extend the Golden Hour for treatment is unclear.Method: Uncontrolled hemorrhagic shock rats and miniature pigs were infused with 0.5, 2, and 5% YQ23 before bleeding was controlled, while Lactate Ringer’s solution (LR) and fresh whole blood plus LR (WB + LR) were set as controls. During hypotensive resuscitation the mean blood pressure was maintained at 50–60 mmHg for 60 min. Hemodynamics, oxygen delivery and utilization, blood loss, fluid demand, organ function, animal survival as well as side effects were observed. Besides, in order to observe whether YQ23 could extend the Golden Hour, the hypotensive resuscitation duration was extended to 180 min and animal survival was observed.Results: Compared with LR, infusion of YQ23 in the 60 min pre-hospital hypotensive resuscitation significantly reduced blood loss and the fluid demand in both rats and pigs. Besides, YQ23 could effectively stabilize hemodynamics, and increase tissue oxygen consumption, increase the cardiac output, reduce liver and kidney injury, which helped to reduce the early death and improve animal survival. In addition, the hypotensive resuscitation duration could be extended to 180 min using YQ23. Side effects such as vasoconstriction and renal injury were not observed. The beneficial effects of 5% YQ23 are equivalent to similar volume of WB + LR.Conclusion: HBOC, such as YQ23, played vital roles in damage-control resuscitation for emergency care and benefited the uncontrolled hemorrhagic shock in the pre-hospital treatment by increasing oxygen delivery, reducing organ injury. Besides, HBOC could benefit the injured and trauma patients by extending the Golden Hour.

Obstetric blood loss: priorities in the choice of infusion solutions

Background. Bleeding accounts for 34 % of maternal mortality. Every 7 minutes 1 woman dies from bleeding during the labour. Retrospective analysis of medical records shows that in 60-80 % of cases, fatal consequences can be avoided. Criteria for defining the concept of “massive blood loss” are the loss of 100 % of circulating blood volume (CBV) within 24 hours or 50 % of CBV within 3 hours, loss of 150 ml/min, of 2 % of body weight within 3 hours, reduction of hematocrit by 10 % in combination with hemodynamic disturbances, one-time blood loss more than 1500-2000 ml or 25-35 % CBV, the need for transfusion of >10 doses of erythromass for 24 hours. The main causes of bleeding in obstetrics include uterine atony, premature placental abruption, uterine rupture, placental abruption, hereditary blood diseases, coagulopathy, sepsis, amniotic fluid embolism. Objective. To describe infusion therapy (IT) for obstetric bleeding. Materials and methods. Analysis of literature data on this issue. Results and discussion. Strategies for the treatment of obstetric hemorrhage include restriction of the traditional massive crystalloid-based IT, applying the principle of antihypertensive resuscitation, using of adequate doses of tranexamic acid, fibrinogen concentrate and prothrombin complex concentrate, early informed use of blood components, and low-volume IT. Routine use of unbalanced crystalloid solutions in critically severe patients is dangerous. Infusion of large amounts of 0.9 % NaCl may cause metabolic hyperchloremic acidosis. Therefore, except in cases of hypochloremia, it is advisable to replace saline with balanced solutions. Reosorbilact (“Yuria-Pharm”) is the most suitable solution for this purpose. It mobilizes the own fluid of the organism, helping it to move from the intercellular space into the vessels. Hypotensive resuscitation involves the introduction of limited amounts of fluid in the early stages of treatment of hemorrhagic shock (until the bleeding stops). Low-volume IT program is a part of hypotensive resuscitation. In this case, the following solutions can be used: Reosorbilact, Sorbilact, Gekoton (“Yuria-Pharm”), 130/0.4 hydroxyethyl starch (HES), hypertonic NaCl solutions (including combined solutions with colloids), polyhydric alcohols. It should be noted that the new generation of HEC has less effect on coagulation than older drugs. Due to the risk of kidney damage, HEC solutions should be used in the lowest effective dose for as shortest period of time as possible. HEC infusion should be stopped as soon as hemodynamic targets are reached. Solutions containing polyhydric alcohols (Reosorbilact, Sorbilact, Xylate) occupy an important position in IT of critically ill patients. Due to their high osmolarity, Reosorbilact and Sorbilact cause fluid to move from the intercellular space into the vascular bed, improving microcirculation and tissue perfusion. The polyhydric alcohol sorbitol contained in these solutions creates increased osmotic pressure in the renal tubules, which provides a diuretic effect. In case of the blood loss volume of I-II functional class up to 1500 ml and stopped bleeding, IT is performed in a limited mode. The volume of intravenous infusion together with blood components should not exceed 200 % of the blood loss volume. Reosorbilact (10-15 ml/kg) is an initial solution in combination with 0.9 % NaCl (20-30 ml/kg). In case of unstable hemodynamics HEC may be added (up to 1,5 L). Blood components are used only in case of confirmed coagulopathy and continued bleeding. In case of massive critical blood loss >1500-2000 ml, it is advisable to use the protocol of massive blood transfusion 1:1:1:1. In order to reduce the pathological response of the endothelium to IT, it is advisable to use a substrate for the nitric oxide synthesis, namely, Tivortin (“Yuria-Pharm”). To stop life-threatening obstetric bleeding, CBV must be refilled using the protocol of massive blood transfusion and automatic blood reinfusion, oxytocin and prostaglandin analogues for the correction of uterine tone, uterine massage, correction of coagulopathy, balloon tamponade of the uterus. Conclusions. 1. Emergency care for massive bleeding in obstetrics is one of the priorities in reducing maternal morbidity and mortality. 2. Intensive therapy of blood loss should be based on modern recommendations and the use of modern drugs. 3. The indications for transfusion of blood components should be clearly applied.