Influence of haemodynamic stabilization with crystalloid and colloidal solutions on cerebral perfusion and integrity during haemorrhagic shock in a large animal model

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A haemorrhagic shock through massive blood loss may occur in several acute or perioperative scenarios. Consequently, die organism is unable to provide effective blood and oxygen supply for its vital organs, which causes severe ischemia. Especially the brain rapidly suffers from ischemia due to limited tolerance, which causes irreversible damages. In the initial treatment several crystalloid or colloid solutions can be administered for fluid resuscitation to restore the microcirculation. This, however, does not necessarily warrant effective microcirculation and organ perfusion. The controversial discussion regarding the most effective solution for fluid resuscitation was recently intensified through the negative risk assessment for the longtime standard colloid hydroxyethyl starch (HES) by the European Medicines Agency. Despite the partial rehabilitation of HES through the German S3-Guideline Intravascular volume therapy in adults, a focus was set on alternative colloids and particularly the well-known gelatin-based solutions. However, for several indications there seems to be a lack of scientific data. Especially the influence of several fluids for treatment of haemorrhagic shock on the cerebral perfusion and integrity is widely unknown. The present research project examines these aspects in a prospective-randomized large animal study. Haemorrhagic shock is induced in anaesthetized pigs and consecutively treated by different solution for fluid resuscitation. Cerebral perfusion is monitored by means of 3-Tesla-MR imaging and arterial spin labeling technique over twelve hours following fluid resuscitation. During this period there will be no intervention in the first three hours. Afterwards heamodynamic and physiological stabilization will be aspired to baseline. To account for the complex disease pattern of haemorrhagic shock additional analyses focus on haemodynamics, coagulopathy, endothelial integrity, inflammatory response and blood gas parameters. Furthermore, the peripheral microcirculation and oxygenation is monitored in real-time. Post-mortem extended immunobiological and histopathological analyses are added. This study, which is closely oriented on clinical reality, assesses the best possible solution for fluid resuscitation regarding regeneration of the impaired organ perfusion.