Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial

Abstract

Background

Intraoperative awareness, without explicit recall, occurs after induction of anaesthesia in approximately 10% of persons under 40 yr of age. Most anaesthetic agents minimally suppress the noradrenergic system. We hypothesised that addition of dexmedetomidine, which suppresses noradrenergic activity, may reduce encephalographic (EEG) arousal in response to tracheal intubation; such an effect would lay the foundation for future studies of dexmedetomidine in reducing intraoperative awareness.

Methods

A single-site randomised, placebo-controlled trial with sex-based stratification was conducted. Participants, aged 18–40 yr old, undergoing intubation for general anaesthesia were eligible for recruitment and randomly allocated to receive dexmedetomidine or placebo. Dexmedetomidine (0.5 μg kg⁻¹) was given as a 5-min loading dose before induction. Bispectral index (BIS) values were collected during the induction phase of anaesthesia and the isolated forearm technique was used to assess patients' responsiveness before and after tracheal intubation. The primary outcome was the effect of dexmedetomidine on changes in BIS from pre-to postintubation.

Results

A total of 51 patients were recruited and included in the primary analysis. We did not observe an effect of dexmedetomidine on changes in BIS after tracheal intubation (mean difference –1.13, 95% confidence interval [CI] –4.87 to 2.62; p=0.556). Dexmedetomidine reduced the estimated plasma propofol concentration at loss of responsiveness (difference [dexmedetomidine – placebo]: –1.06 μg ml⁻¹, 95% CI –1.66 to –0.46; p<0.001) and before intubation (difference [dexmedetomidine – placebo]: –1.84 μg ml⁻¹, 95% CI –2.79 to –0.90; p<0.001). There was one patient in the placebo group who gave positive responses in the isolated forearm test before and after tracheal intubation.

Conclusions

Dexmedetomidine demonstrated an anaesthetic-sparing effect at induction of anaesthesia but did not prevent EEG arousal after tracheal intubation, as defined by an increase in the BIS value.

Clinical Trial Registration

Australia and New Zealand Clinical Trials Registry (Trial ID: ACTRN12622000754741).