Does Propofol Effect Site (Brain) Concentration Predicted by Target-Controlled Infusion Correlate with Propofol Measured in the Brain? An Exploratory Study in Neurosurgical Patients

Abstract

Total intravenous anesthesia with propofol can be administered by target-controlled infusion pumps, which work on the principles of pharmacokinetic modeling. While designing this model, neurosurgical patients were excluded as the surgical site and drug action site remained the same (brain). Whether the predicted set propofol concentration and the actual brain site concentration correlate, especially in neurosurgical patients with impaired blood-brain barrier (BBB), is still unknown. In this study we compared the set propofol effect-site concentration in the target-controlled infusion pump with actual brain concentration measured by sampling the cerebrospinal fluid (CSF). Consecutive adult neurosurgical patients requiring propofol infusion intraoperatively were recruited. Blood and CSF samples were collected simultaneously when patients received propofol infusion at 2 different target effect-site concentrations-2 and 4 ug/mL. To study BBB integrity, CSF-to-blood albumin ratio and imaging findings were compared. The propofol level in the CSF was compared with set concentration using the Wilcoxon signed-rank test. Fifty patients were recruited, and the data were analyzed from 43 patients. There was no correlation between propofol concentration set in TCI and propofol concentration measured in blood and CSF. Though imaging findings were suggestive of BBB disruption in 37/43 patients, the mean (±standard deviation) CSF-to-serum albumin ratio was 0.0028 ± 0.002, suggesting intact BBB integrity (ratio >0.3 was considered as disrupted BBB). CSF propofol level did not correlate with set concentration in spite of acceptable clinical anesthetic effect. Also, the CSF-to-blood albumin measurement did not provide information on the BBB integrity.