CSF sodium at toxic levels precedes delirium in hip fracture patients

Neurotoxicology. 2018 Dec;69:11-16. doi: 10.1016/j.neuro.2018.08.010. Epub 2018 Aug 24.


Delirium is an acute state of confusion and a fluctuating level of consciousness. It is precipitated by physical illness or trauma, such as pneumonia, heart infarction, or hip fracture. Delirium is common among elderly hospitalized patients, and as many as 50% of hip fracture patients may develop delirium. Delirium may precipitate dementia, but recent studies indicate that delirium is caused by unknown neurotoxic mechanisms that are different from those that are associated with dementia. Experimental studies have shown that high extracellular levels of sodium are neurotoxic. We sampled lumbar cerebrospinal fluid (CSF) from hip fracture patients during hip surgery and analyzed metal ions that influence neuronal function. Eight patients who developed delirium after surgery had 21% higher CSF sodium than 17 patients who did not develop delirium (median value 175 mmol/L; range 154-188, vs. 145 mmol/L (112-204; p < 0.008) or 39 patients who underwent elective surgery under spinal anesthesia without developing delirium (145 mmol/L; 140-149; p = 0.0004). Seven patients who had developed delirium before CSF sampling had a median CSF sodium of 150 mmol/L (144-185; p = 0.3). CSF potassium was also 21% higher in patients who developed delirium (p = 0.024), but remained within the physiological range. Serum sodium and potassium were normal in all patient groups. This study, on a small sample of patients, confirms the neurotoxic potential and clinical importance of high extracellular levels of sodium in the brain. High CSF sodium would likely affect cerebral function and could precipitate delirium; further, it could interact with dementia-specific mechanisms to precipitate dementia development.

Keywords: Cerebrospinal fluid; Choroid plexus; Delirium; Potassium; Serum; Sodium.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Delirium / cerebrospinal fluid*
  • Delirium / etiology
  • Delirium / psychology
  • Female
  • Hip Fractures / cerebrospinal fluid*
  • Hip Fractures / psychology
  • Hip Fractures / surgery*
  • Humans
  • Male
  • Middle Aged
  • Postoperative Complications / cerebrospinal fluid*
  • Postoperative Complications / etiology
  • Postoperative Complications / psychology
  • Prospective Studies
  • Sodium / cerebrospinal fluid*
  • Sodium / toxicity*


  • Sodium