Nearly 300,000 Americans suffer cardiac arrest annually. Many die or are severely impaired by neurologic injury, which is worsened by the inflammatory response that develops after reperfusion. In both neurodegenerative diseases and acute brain injury, neuropathology is modified by the composition of the gut microbiome via impaired production of short-chain fatty acids (SCFAs). SCFAs reduce inflammatory cytokine release and constrain the immune response. Whether the composition of the gut microbiome or its metabolites affects neurologic outcome after cardiac arrest (CA) remains unknown.

To determine the relationship between circulating microbial metabolites and neurologic outcome after cardiac arrest (CA).

We performed a single-center, prospective cohort study of comatose CA survivors (n=26) at an urban trauma center. Plasma samples were collected 24 hours after intensive care unit (ICU) admission and gas chromatography-mass spectrometry was used to measure SCFAs. Neurologic outcome was measured with the Cerebral Performance Category (CPC), which was determined at 3 months by a blinded evaluator. Cytotoxic brain edema was analyzed using the Cortex Score from diffusion-weight magnetic resonance imaging (MRI).

The average age was 62 years and time to return of spontaneous circulation (ROSC) was 21.5 minutes. Subjects were predominantly male and had a non-shockable rhythm. In subjects with a good outcome at discharge (CPC 1-2; n=8), plasma levels of SCFAs were significantly higher than in subjects with a poor outcome (CPC 3-5, n=18; all p<0.05). Higher SCFA levels were associated with a reduced cytotoxic brain edema 3-5 days after CA. Higher circulating SCFA level was significantly associated with a good neurologic outcome after adjusting for the MIRACLE-2 score, a validated outcome prediction score in CA (aOR 11.3; 1.2-107.0).

Together, these results suggest that higher circulating SCFAs after CA are independently associated with neurologic outcome after CA and highlight their prognostic and therapeutic potential in this vulnerable population.