Target‐controlled infusion of dexmedetomidine effect‐site concentration for sedation in patients undergoing spinal anaesthesia

Abstract

Dexmedetomidine has been a preferred sedative for patients undergoing regional anaesthesia and is mostly administered via conventional zero-order infusion. Recently, a pharmacokinetic-pharmacodynamic (PKPD) model of dexmedetomidine has been published, but no external validation has been reported in clinical trials. We aimed to administer target-controlled infusion (TCI) of dexmedetomidine at the effect-site concentration (Ce) to patients undergoing spinal anaesthesia and investigate the relationship between dexmedetomidine Ce and the sedative effects. Forty-five patients scheduled for orthopaedic surgery received spinal anaesthesia with 0.5% bupivacaine. After confirmation of sensory block level, we initiated effect-site TCI of dexmedetomidine using Colin's model and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS) with each stepwise increase in the dexmedetomidine Ce. We used a non-linear mixed-effects model to determine the PD relationships between the dexmedetomidine Ce and sedation level. The dexmedetomidine Ce associated with 50% probability (Ce50 ) of the MOAA/S scale ≤4, 3 and 2 was 0.57, 0.89 and 1.19ng/mL, respectively. Mean dexmedetomidine Ce when BIS decreased ≤70 was 0.99±0.15ng/mL. As dexmedetomidine Ce increased, the MOAA/S scale decreased significantly (correlation coefficient [r]=-.832, P<.0001). BIS decreased significantly with increasing dexmedetomidine Ce (r=-.811, P<.0001) and decreasing MOAA/S scale (r=.838, P<.0001). The most common side effects were hypertension (26.67%) and bradycardia (20%). We applied effect-site TCI of dexmedetomidine in patients undergoing spinal anaesthesia for the first time. Dexmedetomidine Ce correlated significantly with MOAA/S scale and BIS, and was 0.89 and 1.19ng/mL for moderate and deep sedation, respectively.