Time-course relationship between cerebrospinal fluid and serum concentrations of midazolam and albumin in patients with cardiac arrest undergoing targeted temperature management.

Aim: To understand the serum and cerebrospinal fluid (CSF) distribution of midazolam is important for proper timing of neurological prognostication of targeted temperature management(TTM) patients. Midazolam binds extensively to albumin in serum although non protein bound form exist in CSF. We investigated the time-course of CSF, serum concentrations of midazolam and albumin in patients with cardiac arrest who underwent TTM.

Methods: This prospective, single-center, observational study was conducted between May 2020 and April 2022. Midazolam and albumin concentrations in CSF and serum were quantified 0, 24, 48, and 72 h after the return of spontaneous circulation for comparison between the good (Cerebral Performance Category (CPC) 1 and 2) and poor (CPC 3, 4, and 5) neurologic outcome groups. The CSF/serum (C/S) ratios of midazolam and albumin concentrations were determined, along with their correlation coefficients.

Results: Of the 19 enrolled patients, 13 experienced poor outcomes. At 0 h, serum midazolam concentrations were the lowest, whereas serum albumin levels were the highest; in the CSF, the concentrations of both peaked at 24 h. There were no significant inter-group differences in midazolam concentrations in CSF or serum. The C/S ratios of midazolam and albumin significantly differed between the groups. Moderate to strong positive correlations were observed between the midazolam and albumin C/S ratios.

Conclusion: In CSF, midazolam and albumin concentrations peaked 24 h post-cardiac arrest. Midazolam and albumin C/S ratios were significantly higher in the poor outcome group and positively correlated with each other, suggesting blood-brain barrier disruption 24 h post-cardiac arrest.