Dexmedetomidine-Ketamine-Based Multimodal General Anesthesia with Electroencephalographic Spectrogram-Guided...

Older adults undergoing lumbar spine fusion are vulnerable to impaired postoperative recovery and persistent postsurgical pain. Dexmedetomidine-ketamine-based multimodal general anesthesia may reduce volatile anesthetic and opioid exposure, but its efficacy and tolerability in older adults undergoing high-pain spine surgery remain uncertain. This randomized controlled trial evaluated whether electroencephalographic spectrogram-guided multimodal general anesthesia improves early recovery compared with conventional balanced anesthesia.

Patients aged ≥60 years undergoing elective lumbar spine fusion were randomized 1:1 in a parallel-group, superiority design to receive either dexmedetomidine-ketamine-based multimodal general anesthesia guided by electroencephalographic density spectral array monitoring or conventional bispectral index-guided balanced anesthesia. All patients received standardized perioperative care. The primary efficacy outcome was the 24-hour change in Quality of Recovery-15 (QoR-15) score from baseline, analyzed as the between-group difference in mean change score. Secondary outcomes included opioid requirements, 3-month pain outcomes, and safety and tolerability outcomes. All secondary outcomes, including the 3-month pain outcomes, were exploratory.

Among 100 randomized patients, 50 were assigned to each group. The multimodal general anesthesia group had a smaller 24-hour decline in QoR-15 score than the control group (-22.5 vs -33.5 points; mean difference, 11.0; 95% confidence interval, 0.8-21.2; p=0.036). Multimodal general anesthesia reduced sevoflurane consumption [28 (22-42) vs 43 (36-53) mL; p<0.001], intraoperative fentanyl dose [150 (100-200) vs 200 (125-250) μg; p=0.003], and post-anesthetic care unit morphine requirement [0 (0-2) vs 2 (0-3) mg; p<0.001], at the expense of increased intraoperative norepinephrine and atropine requirements. No significant between-group differences were observed in postoperative safety outcomes, although the trial was not powered to exclude clinically relevant differences. Exploratory 3-month analyses showed lower average pain intensity in the multimodal general anesthesia group [1 (0-2) vs 2 (0-4); p=0.033], whereas the proportion of pain-free patients did not differ significantly [41.7% vs 28.0%; p=0.203].

Dexmedetomidine-ketamine-based multimodal general anesthesia implemented with spectrogram-guided titration improved early patient-centered recovery and reduced immediate perioperative opioid requirements, at the expense of increased intraoperative vasopressor and atropine use. Exploratory analyses suggested a possible reduction in 3-month average pain intensity, which requires confirmation in trials adequately powered for persistent postsurgical pain.

NCT05247177.