bioRxivPharmacology & ToxicologyPreprint
Intramuscular adrenaline administration does not improve a survival period on rats with crush syndrome despite short-term hemodynamic support and renal protection
Abstract
Crush syndrome (CS) is a serious medical condition characterized by damage to the muscle cells due to pressure and is associated with high mortality, even in patients receiving fluid therapy. We focused on adrenaline (Adr), a standard medication administered by medical teams dispatched during disasters. Adr is readily available for use in disaster scenarios owing to its inclusion in standard emergency kits. The effectiveness of Adr in the treatment of CS remains a subject of ongoing debate. This study aimed to evaluate the impact of Adr on acute complications, such as heart failure, shock, and renal failure, and explore whether its influence on inflammatory pathways is correlated with improved survival in rats with CS. The CS model involved subjecting anesthetized rats to bilateral hindlimb compression using a rubber tourniquet for 5 h. Subsequently, the rats were randomly divided into eight groups. Under continuous monitoring and recording of the arterial blood pressure, blood and tissue samples were collected for biochemical analyses at designated time points before and after reperfusion. The survival rate, vital signs, and blood gas parameters were higher in the CS group than in the sham group. They were improved in the Adr-treated group (0.01 or 0.01 mg/kg), which was not significantly different from that in the CS group, despite the improvement in shock and kidney dysfunction. In conclusion, intramuscular Adr provides immediate hemodynamic stabilization and renal protection during the early stages of CS. However, its use requires careful dose titration; low doses may promote the systemic release of lethal toxins, whereas high doses may worsen metabolic acidosis. These findings highlight the importance of combining Adr with other therapies, such as fluid resuscitation, to manage systemic toxemia inherent in CS.
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