Serum netrin-1 levels at presentation and delayed neurological sequelae in unintentional carbon monoxide poisoning

<b>Objectives:</b> The early identification of patients with a high risk of developing delayed neurological sequelae (DNS) can improve the quality of care in carbon monoxide (CO) poisoning cases. The aim of this study is to investigate whether the serum netrin-1 levels measured at presentation to the emergency department (ED) predicted the development of DNS after acute CO intoxication. <b>Methods:</b> This prospective observational study was conducted between 1 August 2018 and 31 July 2019 in a single tertiary hospital. The patients with acute CO intoxication and serum netrin-1 levels measured at the time of ED presentation were included in the study. All patients were followed up for six weeks regarding the development of DNS. The patients were divided into two groups, including those who developed DNS (DNS group) and those who did not (non-DNS group). <b>Results:</b> A total of 183 patients were included in the study, and 54 (29.5%) developed DNS. The median serum netrin-1 level at ED presentation was significantly lower in the DNS group (391.5 pg/mL [263.0–550.5]) than in the non-DNS group (626.0 pg/mL [505.9–755.6]) (<i>p</i> &lt; .001). Multivariate analysis revealed that a low serum netrin-1 level (adjusted odds ratio [AOR]: 8.02, 95% CI: 2.45–26.20), low Glasgow coma scale (GCS) score at ED presentation (AOR: 0.81, 95% CI: 0.68–0.97), long CO exposure time (AOR: 1.96, 95% CI: 1.49–2.56), and the presence of acute brain lesions (AOR: 8.24, 95% CI: 2.37–28.58) on diffusion-weighted imaging were independent predictors of DNS. Serum netrin-1 levels less than 432 pg/mL predicted the development of DNS with a sensitivity of 68.5% (95% CI: 54.4%-80.5%) and a specificity of 86.0% (95% CI: 78.8%-91.5%). <b>Conclusions:</b> Low serum netrin-1 levels were significantly associated with the development of DNS. Therefore, serum netrin-1 at ED presentation can help identify patients at risk of developing DNS following discharge.

**研究目标**：早期识别存在迟发性神经后遗症（delayed neurological sequelae, DNS）高风险的患者，可提升一氧化碳（carbon monoxide, CO）中毒病例的诊疗质量。本研究旨在探讨急诊（emergency department, ED）就诊时检测的血清netrin-1水平是否可预测急性一氧化碳中毒后迟发性神经后遗症的发生。**研究方法**：本研究为一项前瞻性观察性研究，于2018年8月1日至2019年7月31日在单家三级医院开展。纳入确诊急性一氧化碳中毒且于急诊就诊时完成血清netrin-1水平检测的患者。对所有患者进行为期6周的随访，监测迟发性神经后遗症的发生情况。根据是否发生DNS，将患者分为DNS组与非DNS组。**研究结果**：本研究共纳入183例患者，其中54例（29.5%）发生迟发性神经后遗症。急诊就诊时的血清netrin-1水平中位数在DNS组为391.5 pg/mL [263.0–550.5]，显著低于非DNS组的626.0 pg/mL [505.9–755.6]（p < 0.001）。多因素分析显示，低血清netrin-1水平（校正比值比[AOR]：8.02，95%置信区间[CI]：2.45–26.20）、急诊就诊时较低的格拉斯哥昏迷量表（Glasgow coma scale, GCS）评分（AOR：0.81，95%CI：0.68–0.97）、较长的一氧化碳暴露时长（AOR：1.96，95%CI：1.49–2.56）以及弥散加权成像（diffusion-weighted imaging）检出急性脑病变（AOR：8.24，95%CI：2.37–28.58）均为迟发性神经后遗症发生的独立预测因素。当血清netrin-1水平低于432 pg/mL时，预测迟发性神经后遗症发生的灵敏度为68.5%（95%CI：54.4%–80.5%），特异度为86.0%（95%CI：78.8%–91.5%）。**研究结论**：低血清netrin-1水平与迟发性神经后遗症的发生显著相关。因此，急诊就诊时检测的血清netrin-1水平可辅助识别出院后发生迟发性神经后遗症风险较高的患者。