Infusion of sodium DL-3-ß-hydroxybutyrate decreases cerebral injury biomarkers after resuscitation in experimental cardiac arrest

Crit Care. 2024 Sep 20;28(1):314. doi: 10.1186/s13054-024-05106-8.

Abstract

Aims: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA.

Results: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals.

Conclusions: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude.

Keywords: Anoxic injury; Beta hydroxybutyrate; Cardiac arrest; Ischemia–reperfusion; Ketone bodies.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Animals
  • Biomarkers* / analysis
  • Biomarkers* / blood
  • Brain Injuries / drug therapy
  • Cardiopulmonary Resuscitation* / methods
  • Disease Models, Animal*
  • Heart Arrest* / complications
  • Heart Arrest* / drug therapy
  • Heart Arrest* / therapy
  • Male
  • Sodium Oxybate / administration & dosage
  • Sodium Oxybate / pharmacology
  • Sodium Oxybate / therapeutic use
  • Swine

Substances

  • Biomarkers
  • Sodium Oxybate
  • 3-Hydroxybutyric Acid