# Effect of the addition of a low-dose of ketamine to propofol anaesthesia on the phase-amplitude coupling features of an electroencephalogram

## TL;DR

Adding low-dose ketamine to propofol anesthesia changes EEG patterns, specifically altering the preferred phase of phase-amplitude coupling.

## Contribution

The study reveals how low-dose ketamine affects EEG phase-amplitude coupling during propofol-based anesthesia, offering insights for monitoring hypnotic depth.

## Key findings

- EEG modulation index remained stable after ketamine administration.
- Preferred phase shifted significantly from 88° to 29° after ketamine infusion.
- Findings suggest phase-amplitude coupling analysis could improve hypnotic depth monitoring.

## Abstract

Low-dose ketamine as an adjunct to propofol-based total intravenous anaesthesia (TIVA) complicates hypnotic depth monitoring by increasing bispectral index values and altering electroencephalogram (EEG). Phase-amplitude coupling is a promising EEG marker of anaesthesia-induced unconsciousness, but its response to ketamine during TIVA remains unclear. Understanding this interaction may improve hypnotic depth monitoring under multimodal anaesthesia. This study aimed to investigate the effect of low-dose ketamine on EEG modulation index and preferred phase under propofol-based total intravenous . anaesthesia.

This prospective observational study analysed 19 patients (age 28–66 yr, American Society of Anesthsiology physical status 1 or 2) who underwent surgery during TIVA with propofol. After confirming the stability of propofol infusion, low-dose ketamine (0.5 mg kg−1) was administered as a bolus, followed by continuous infusion at a rate of 0.125 mg kg−1 h−1. Frontal EEG was analysed at baseline (PreKet) and at 10 min (PostKet1) and 20 min (PostKet2) after ketamine administration.

Analysis of delta-alpha phase-amplitude coupling revealed that the EEG modulation index (×103) remained stable across the study period: 0.47 (95% confidence interval: 0.25–0.69) at PreKet, 0.46 (0.20–0.73) at PostKet1, and 0.35 (0.15–0.55) at PostKet2 (P=0.623). However, the mean preferred phase, representing the delta wave phase at which the alpha oscillation amplitude was maximal, exhibited a significant shift from 88° (95% confidence interval: 50°–126°) at PreKet to 29° (95% confidence interval: −10° to 69°) at PostKet2 (P=0.021).

This study demonstrates the effect of low-dose ketamine on EEG phase-amplitude coupling during total intravenous anaesthesia with propofol. Our findings provide new insights into the neural mechanisms of low-dose ketamine and support the feasibility of phase-amplitude coupling analysis as a potential tool for improving hypnotic depth monitoring in clinical practice.

UMIN000050331.