Introduction: Delirium occurs in ~70% of older ICU patients and is associated with an increased risk of subsequent long-term cognitive impairment. Although evidence from animal models and human plasma biomarkers suggest a role for blood-brain barrier (BBB) dysfunction in delirium, its role in ICU delirium is unclear. Here, we evaluated cerebrospinal fluid (CSF)-to-plasma albumin ratio (CPAR) and urea (CPUR) to investigate the role of BBB dysfunction in ICU delirium among older ICU patients on mechanical ventilation and/or vasopressors. Methods: Patients were included from Complement Activation in Delirium and Subsequent Cognitive Impairment and Alzheimer’s Disease in the ICU (CASCADE-ICU) study. CASCADE-ICU is an ongoing prospective cohort study that aims to determine the relationship of CSF complement activation with ICU delirium and subsequent dementia. In CASCADE-ICU, patients aged ≥ 65-years on mechanical ventilation and/or vasopressors undergo study LP (for CSF sampling) and blood sampling ≤72 hours after ICU admission. Exclusions include known acute brain injury, severe dementia, or LP contraindications. Delirium was assessed with Confusion Assessment Method (CAM) for the Intensive Care Unit (CAM-ICU; non-verbal) or 3-Minute Diagnostic CAM (3D-CAM; verbal) twice daily. A Richmond Agitation Sedation Scale score ≤ -4 was considered coma. A Beckman DxC 600 clinical analyzer measured albumin and urea levels. Spearman correlation of CPAR and CPUR with duration of delirium and/or coma was calculated. Results: Of the 27 patients included, 19 (70.4%) experienced delirium. Mean age was 75.4 years with 63% female and 81.5% White. The most common ICU admission diagnosis was septic shock (52%), followed by respiratory failure (22%). CPAR was not correlated with CPUR (ρ=0.292, p=0.137), but was correlated with delirium and/or coma duration (ρ=0.386, p=0.047). CSF urea levels were correlated with delirium and/or coma duration (ρ=0.444, p=0.021), but CPUR was not (ρ=0.358, p=0.0664). Conclusions: CPAR and CPUR may be distinct markers of BBB dysfunction in older ICU patients. Increased BBB permeability at ICU admission may play a role in ICU delirium, but further work using a panel of BBB markers in larger cohorts of ICU patients is needed to clarify these mechanisms.
Popowicz et al. (Sun,) studied this question.