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Electroencephalographic-based monitoring systems such as the bispectral index (BIS) may reduce anaesthetic overdose rates.We hypothesised that goal-directed sevoflurane administration (guided by BIS monitoring) could reduce the sevoflurane plasma concentration (SPC) and intraoperative vasopressor doses during on-pump cardiac surgery.A prospective, controlled, sequential two-arm clinical study.German university medical centre with more than 2500 cardiac surgery interventions per year.Sixty elective on-pump cardiac surgery patients.In group Sevo1.8% (n = 29), the sedation depth was maintained with a sustained inspired concentration of sevoflurane 1.8% before and during cardiopulmonary bypass (CPB). In group SevoBIS (n = 31), the inspired sevoflurane concentration was titrated to maintain a BIS target between 40 and 60.SPC during CPB and the intraoperative administration of noradrenaline. Additional analyses were performed on intraoperative awareness, postoperative blood lactate concentration, duration of mechanical ventilation, intensive care unit length of stay and kidney injury.Mean inspired sevoflurane concentration was 0.8% in group SevoBIS, representing a 57.1% reduction (P < 0.001) compared with group Sevo1.8%. The mean SPC was 42.3 μg ml−1 [95% confidence interval (CI) 40.0 to 44.6] in group Sevo1.8% and 21.0 μg ml−1 (95% CI 18.8 to 23.3) in group SevoBIS, representing a 50.2% reduction (P < 0.001). During CPB, the mean cumulative dose of noradrenaline administered was 13.48 μg kg−1 (95% CI 10.52 to 17.19) in group Sevo1.8% and 4.06 μg kg−1 (95% CI 2.67 to 5.97) in group SevoBIS (P < 0.001). Pearson's correlation coefficient (between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose) was 0.607 (P < 0.001). No intraoperative awareness signs were detected.BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery.