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

BJA open Pub Date : 2025-09-12 DOI:10.1016/j.bjao.2025.100486

Ryusuke Tanaka, Masahide Kaneko, Masaki Takekoshi, Satoshi Tanaka

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Clinical trial registration

UMIN000050331.

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在异丙酚麻醉中加入低剂量氯胺酮对脑电图相幅耦合特征的影响

背景：低剂量氯胺酮作为以异丙酚为基础的全静脉麻醉（TIVA）的辅助药物，通过增加双谱指数值和改变脑电图（EEG）使催眠深度监测复杂化。相幅耦合是一种很有前景的麻醉无意识的脑电图标记物，但其在TIVA期间对氯胺酮的反应尚不清楚。了解这种相互作用可以改善多模态麻醉下的催眠深度监测。本研究旨在探讨低剂量氯胺酮对异丙酚全静脉注射下脑电调制指数和首选相的影响。麻醉。方法本前瞻性观察研究分析了19例使用异丙酚进行TIVA手术的患者（年龄28-66岁，美国麻醉学会物理状态1或2）。在确认异丙酚输注的稳定性后，将低剂量氯胺酮（0.5 mg kg - 1）作为小丸给药，然后以0.125 mg kg - 1 h - 1的速率持续输注。分析氯胺酮给药后基线（PreKet）、10min （PostKet1）和20min （PostKet2）额叶脑电图。结果δ - α相幅耦合分析显示，脑电调制指数（×103）在整个研究期间保持稳定：PreKet为0.47(95%可信区间：0.25 ~ 0.69)，PostKet1为0.46 (0.20 ~ 0.73)，PostKet2为0.35 (0.15 ~ 0.55)（P=0.623）。然而，平均首选相位，代表α振荡幅度最大的δ波相位，显示出从PreKet的88°（95%置信区间：50°-126°）到PostKet2的29°（95%置信区间：−10°至69°）的显著变化（P=0.021）。结论低剂量氯胺酮对异丙酚全静脉麻醉时脑电图相幅耦合的影响。我们的研究结果为低剂量氯胺酮的神经机制提供了新的见解，并支持相幅耦合分析作为临床实践中改善催眠深度监测的潜在工具的可行性。临床试验注册号：umin000050331。

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