Postoperative delirium and changes in the bloodebrain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study

Background: Case-control studies have associated delirium with bloodebrain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity. Methods: Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate. Results: The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR rho= 0.78, P=0.01; S100B rho= 0.41, P<0.001), delirium incidence (CPAR P= 0.012; S100B P<0.001) and CSF IL-6 (CPAR rho=0.66 P=0.04; S100B rho= 0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (rho= 0.64, P= 0.04), S100B (rho=0.70, P<0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (rho=0.36, P=0.01). Conclusion: Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB.

Automated summary

This study found that changes in cerebrospinal fluid/plasma albumin ratio and plasma S100B during the perioperative period were associated with the severity of delirium. The breakdown of the blood-brain barrier was identified as a cause of postoperative delirium. Blood loss was also found to be related to the occurrence and severity of delirium.