Effects of remifentanil on brain responses to noxious stimuli during deep propofol sedation

Br J Anaesth. 2023 Feb;130(2):e330-e338. doi: 10.1016/j.bja.2022.06.038. Epub 2022 Aug 13.


Background: The safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing.

Methods: Optimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml-1), medium (1 ng ml-1), and high (1.5 ng ml-1) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness.

Results: At low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed.

Conclusions: The response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress.

Keywords: deep sedation; functional MRI; neuroimaging; nociception; pain; propofol; remifentanil.

MeSH terms

  • Anesthetics, Intravenous / pharmacology
  • Brain
  • Electroencephalography
  • Humans
  • Pain
  • Piperidines / pharmacology
  • Propofol* / pharmacology
  • Remifentanil / pharmacology
  • Unconsciousness


  • Propofol
  • Remifentanil
  • Piperidines
  • Anesthetics, Intravenous