BACKGROUND: 

Ketamine is typically used by anesthesiologists as an adjunct for general anesthesia and as a nonopioid analgesic. It has been explored for prevention of postoperative delirium, although results have been contradictory. In this study, we investigated the association of ketamine with postoperative delirium and specific encephalographic signatures. Furthermore, we examined these associations in the context of baseline neurocognition as measured by a validated assessment.

METHODS: 

We conducted a prospective observational study from January 2019 to December 2020. Ninety-eight patients aged ≥65 years and undergoing spine surgery scheduled for ≥3 hours were included in the study. All participants who completed the University of California San Francisco (UCSF) Brain Health Assessment preoperatively and postoperatively were assessed with the confusion assessment method for intensive care unit (CAM-ICU) and/or the Nursing Delirium Screening Scale (NuDESC). Patients had frontal electroencephalogram (EEG) recordings (SedLine Root, Masimo, Corp) quantitatively analyzed. We used 60 seconds of artifact-free EEG (without burst suppression) extracted from the middle of the maintenance period to calculate the normalized power spectral density (PSD). Comparisons were made between those who did or did not receive ketamine and according to results from neurocognitive assessments.

RESULTS: 

Ninety-eight patients (of a total of 155, enrolled and consented) had EEG of sufficient quality for analysis (42 women). Overall, we found a significant increase in the EEG power in the moderate frequency range (10–20 Hz) in patients that received ketamine. When the patients were divided by their preoperative cognitive status, this result in the ketamine group only held true for the cognitively normal patients. Patients that were cognitively impaired at baseline did not demonstrate a significant change in EEG characteristics based on ketamine administration, but impaired patients that received ketamine had a significantly higher rate of postoperative delirium (52% ketamine versus 20% no ketamine) (odds ratio [OR], 4.36; confidence interval [CI], 1.02–18.22; P = .048). In patients determined to be preoperatively cognitively normal, the incidence of postoperative delirium was not significantly associated with ketamine administration (19% ketamine versus 17% no ketamine) (OR, 1.10; CI, 0.30–4.04; P = .5833).

CONCLUSIONS: 

Ketamine-related changes in EEG are observed in a heterogeneous group of patients receiving spine surgery. This result was driven primarily by the effect of ketamine on cognitively normal patients and not observed in patients that were cognitively impaired at baseline. Furthermore, patients who were cognitively impaired at baseline and who had received ketamine were more likely to develop postoperative delirium, suggesting that cognitive vulnerability might be predicted by the lack of a neurophysiologic response to ketamine.

中文翻译：

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有和没有术前认知障碍的老年患者的氯胺酮相关术中脑电图特征

背景： 

氯胺酮通常被麻醉师用作全身麻醉的辅助剂和非阿片类镇痛剂。它已被探索用于预防术后谵妄，尽管结果相互矛盾。在这项研究中，我们调查了氯胺酮与术后谵妄和特定脑电图特征的关系。此外，我们在通过经过验证的评估测量的基线神经认知的背景下检查了这些关联。

方法： 

我们于 2019 年 1 月至 2020 年 12 月进行了一项前瞻性观察性研究。该研究纳入了 98 名年龄≥65 岁且接受脊柱手术时间≥3 小时的患者。所有在术前和术后完成加州大学旧金山分校 (UCSF) 脑健康评估的参与者都使用重症监护病房 (CAM-ICU) 和/或护理谵妄筛查量表 (NuDESC) 的混乱评估方法进行了评估。对患者的额叶脑电图 (EEG) 记录 (SedLine Root, Masimo, Corp) 进行了定量分析。我们使用从维护期中间提取的 60 秒无伪影 EEG（无突发抑制）来计算归一化功率谱密度 (PSD)。

结果： 

98 名患者（总共 155 名，登记并同意）具有足够质量的脑电图进行分析（42 名女性）。总体而言，我们发现接受氯胺酮治疗的患者在中等频率范围（10-20 Hz）的脑电图功率显着增加。当患者按术前认知状态进行划分时，氯胺酮组的这一结果仅适用于认知正常的患者。基线时认知受损的患者在服用氯胺酮后脑电图特征没有显着变化，但接受氯胺酮治疗的受损患者术后谵妄发生率显着升高（52% 氯胺酮对 20% 未使用氯胺酮）（优势比 [OR ]，4.36；置信区间 [CI]，1.02–18.22；P= .048)。在被确定为术前认知正常的患者中，术后谵妄的发生率与氯胺酮给药没有显着相关性（19% 氯胺酮对 17% 没有氯胺酮）（OR，1.10；CI，0.30-4.04；P = .5833）。

结论： 

在接受脊柱手术的一组异质患者中观察到与氯胺酮相关的脑电图变化。这一结果主要是由于氯胺酮对认知正常患者的影响，而在基线认知受损的患者中未观察到。此外，基线时认知受损且接受过氯胺酮治疗的患者更有可能发生术后谵妄，这表明认知脆弱性可能是由于对氯胺酮缺乏神经生理反应而导致的。