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

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 noradrenerg...

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Main Authors: Kaitlin Kramer, Thomas Payne, Mitchell Brooks, Jessica Barry, Neha Mahajan, Samantha Malcolm, Hannah Braithwaite, Alex Wang, Chris Thompson, Keith Liyanagama, Robert D. Sanders
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:BJA Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772609624001096
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author Kaitlin Kramer
Thomas Payne
Mitchell Brooks
Jessica Barry
Neha Mahajan
Samantha Malcolm
Hannah Braithwaite
Alex Wang
Chris Thompson
Keith Liyanagama
Robert D. Sanders
author_facet Kaitlin Kramer
Thomas Payne
Mitchell Brooks
Jessica Barry
Neha Mahajan
Samantha Malcolm
Hannah Braithwaite
Alex Wang
Chris Thompson
Keith Liyanagama
Robert D. Sanders
author_sort Kaitlin Kramer
collection DOAJ
description 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).
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spelling doaj-art-76989d87cace43fd8a79e28a719324342025-08-20T02:54:07ZengElsevierBJA Open2772-60962025-03-011310035910.1016/j.bjao.2024.100359Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trialKaitlin Kramer0Thomas Payne1Mitchell Brooks2Jessica Barry3Neha Mahajan4Samantha Malcolm5Hannah Braithwaite6Alex Wang7Chris Thompson8Keith Liyanagama9Robert D. Sanders10Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; The Royal Melbourne Hospital, Melbourne, VIC, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, AustraliaDepartment of Anaesthetics, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Corresponding author.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).http://www.sciencedirect.com/science/article/pii/S2772609624001096accidental awareness under general anaesthesiaanaesthesiaconnected consciousnessdexmedetomidinesurgery
spellingShingle Kaitlin Kramer
Thomas Payne
Mitchell Brooks
Jessica Barry
Neha Mahajan
Samantha Malcolm
Hannah Braithwaite
Alex Wang
Chris Thompson
Keith Liyanagama
Robert D. Sanders
Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
BJA Open
accidental awareness under general anaesthesia
anaesthesia
connected consciousness
dexmedetomidine
surgery
title Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
title_full Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
title_fullStr Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
title_full_unstemmed Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
title_short Noradrenergic suppression to reduce electroencephalographic arousal after intubation: a randomised, placebo-controlled trial
title_sort noradrenergic suppression to reduce electroencephalographic arousal after intubation a randomised placebo controlled trial
topic accidental awareness under general anaesthesia
anaesthesia
connected consciousness
dexmedetomidine
surgery
url http://www.sciencedirect.com/science/article/pii/S2772609624001096
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