Breathe–squeeze: pharmacodynamics of a stimulus-free behavioural paradigm to track conscious states during sedation☆

Background Conscious states are typically inferred through responses to auditory tasks and noxious stimulation. We report the use of a stimulus-free behavioural paradigm to track state transitions in responsiveness during dexmedetomidine sedation. We hypothesised that estimated dexmedetomidine effect-site (Ce) concentrations would be higher at loss of responsiveness (LOR) compared with return of responsiveness (ROR), and both would be lower than comparable studies that used stimulus-based assessments. Methods Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine data were analysed for secondary analysis. Fourteen healthy volunteers were asked to perform the breathe–squeeze task of gripping a dynamometer when inspiring and releasing it when expiring. LOR was defined as five inspirations without accompanied squeezes; ROR was defined as the return of five inspirations accompanied by squeezes. Brain states were monitored using 64-channel EEG. Dexmedetomidine was administered as a target-controlled infusion, with Ce estimated from a pharmacokinetic model. Results Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml−1; 95% confidence interval: 0.69–1.15) than at ROR (1.43 ng ml−1; 95% confidence interval: 1.27–1.58) (paired t-test; P=0.002). LOR was characterised by progressively increasing fronto-occipital EEG power in the 0.5–8 Hz band and loss of occipital alpha (8–12 Hz) and global beta (16–30 Hz) power. These EEG changes reverted at ROR. Conclusions The breathe–squeeze task can effectively track changes in responsiveness during sedation without external stimuli and might be more sensitive to state changes than stimulus-based tasks. It should be considered when perturbation of brain states is undesirable. Clinical trial registration NCT04206059.