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.