Effect of fluid resuscitation on cerebral integrity A prospective randomised porcine study of haemorrhagic shock

BACKGROUND The treatment of haemorrhagic shock is a challenging task. Colloids have been regarded as standard treatment, but their safety and benefit have been the subject of controversial debates. Negative effects, including renal failure and increased mortality, have resulted in restrictions on their administration. The cerebral effects of different infusion regimens are largely unknown. OBJECTIVES The current study investigated the impact of gelatine-polysuccinate, hydroxyethyl starch (HES) and balanced electrolyte solution (BES) on cerebral integrity, focusing on cerebral inflammation, apoptosis and blood flow in pigs. DESIGN Randomised experimental study. SETTING University-affiliated large animal research unit. ANIMALS Twenty-four juvenile pigs aged 8 to 12 weeks. INTERVENTION Haemorrhagic shock was induced by controlled arterial blood withdrawal to achieve a combination of relevant blood loss (30 to 40 ml kg(-1)) and haemodynamic deterioration. After 30 min of shock, fluid resuscitation was started with either gelatine-polysuccinate, HES or BES. The animals were then monitored for 4 h. MAIN OUTCOME MEASURES Cerebral perfusion and diffusion were measured via arterial-spin-labelling MRI. Peripheral tissue perfusion was evaluated via white light spectroscopy. Cortical and hippocampal samples were collected at the end of the experiment. The numbers of cerebral cell nuclei were counted and mRNA expression of markers for cerebral apoptosis [glucose transporter protein type 1 (SLC2A), lipocalin 2 (LCN-2), aquaporin-4 (AQP4)] and inflammation [IL-6, TNF-alpha, glial fibrillary acidic protein (GFAP)] were determined. RESULTS The three fluid protocols all stabilised the macrocirculation. Fluid resuscitation significantly increased the cerebral perfusion. Gelatine-polysuccinate and HES initially led to a higher cardiac output but caused haemodilution. Cerebral cell counts (as cells mu m(-2)) were lower after colloid administration in the cortex (gelatine-polysuccinate, 1.8 +/- 0.3; HES, 1.9 +/- 0.4; each P < 0.05 vs. BES, 2.3 +/- 0.2) and the hippocampus (gelatine-polysuccinate, 0.8 +/- 0.2; HES, 0.9 +/- 0.2; each P < 0.05 vs. BES, 1.1 +/- 0.1). After gelatine-polysuccinate, the hippocampal SLC2A and GFAP were lower. After gelatine-polysuccinate, the cortical LCN-2 and TNF-alpha expression levels were increased (each P < 0.05 vs. BES). CONCLUSION In a porcine model, fluid resuscitation by colloids, particularly gelatine-polysuccinate, was associated with the occurrence of cerebral injury. ETHICAL APPROVAL NUMBER 23 177-07/G 15-1-092; 01/2016.

Automated summary

In this study using a porcine model, fluid resuscitation with colloids, particularly gelatine-polysuccinate, was associated with cerebral injury.