BackgroundCrush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from decompression after compression (i.e., ischemia/reperfusion injury). A large number of CS patients develop cardiac failure, kidney dysfunction, and systemic inflammation, even when fluid therapy is administered. We evaluated whether the administration of astragaloside-IV (AS)-containing fluid improved survival by preventing kidney and muscular mitochondrial dysfunction in a rat model of CS.ResultsThe CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into four groups: (1) sham; (2) CS with no treatment; (3) CS with normal saline treatment; and (4) CS with normal saline + 10 mg/kg AS. AS-containing fluid improved kidney function by improving shock and metabolic acidosis in CS rats. In addition, there was a reduction in oxidative damage. The attenuation of hyperkalemia was significantly related to improving muscle injury via preventing mitochondrial dysfunction. Moreover, this mitochondria protection mechanism was related to the nitric oxide (NO) generated by activation of endothelial nitric oxide synthase, which provided an anti-oxidative and anti-inflammatory effect.ConclusionsTreatment with AS-containing fluid led to a dramatic improvement in survival following CS because of direct and indirect anti-oxidative effects in the kidney, and improvements in mitochondrial dysfunction and inflammation owing to AS acting as an NO donor in injured muscle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0313-2) contains supplementary material, which is available to authorized users.