PURPOSE Withholding parenteral nutrition (PN) early in critical illness, late-PN, has shown to prevent infections despite a higher peak C-reactive protein (CRP). We investigated whether the accentuated CRP rise was caused by a systemic inflammatory effect mediated by cytokines or arose as a consequence of the different feeding regimens, and whether it related to improved outcome with late-PN. METHODS This secondary analysis of the EPaNIC-RCT first investigated, with multivariable linear regression analyses, determinants of late-PN-induced CRP rise and its association with cytokine responses (IL-6, IL-10, TNF-α) in matched early-PN and late-PN patients requiring intensive care for ≥ 3 days. Secondly, with multivariable logistic regression and Cox proportional-hazard analyses, we investigated whether late-PN-induced CRP rises mediated infection prevention and enhanced recovery or reflected an adverse effect counteracting such benefits of late-PN. RESULTS CRP peaked on day 3, higher with late-PN [216(152-274)mg/l] (n = 946) than with early-PN [181(122-239)mg/l] (n = 946) (p < 0.0001). Independent determinants of higher CRP rise were lower carbohydrate and protein intakes (p ≤ 0.04) with late-PN, besides higher blood glucose and serum insulin concentrations (p ≤ 0.01). Late-PN did not affect cytokines. Higher CRP rises were independently associated with more infections and lower likelihood of early ICU discharge (p ≤ 0.002), and the effect size of late-PN versus early-PN on these outcomes was increased rather than reduced after adjusting for CRP rise, not confirming a mediating role. CONCLUSIONS The higher CRP rise with late-PN, explained by the early macronutrient deficits, did not relate to cytokine responses and thus did not reflect more systemic inflammation. Instead of mediating clinical benefit on infection or recovery, the accentuated CRP rise appeared an adverse effect reducing such late-PN benefits.

中文翻译：

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C 反应蛋白升高以应对危重病早期的常量营养素缺乏：炎症的迹象或感染预防和恢复的介质。

目的 尽管 C 反应蛋白 (CRP) 峰值较高，但在危重疾病早期停止肠外营养 (PN)，晚期 PN 已显示可预防感染。我们研究了 CRP 升高的加剧是由细胞因子介导的全身炎症效应引起的，还是由不同的喂养方案引起的，以及它是否与晚期 PN 的预后改善有关。方法 该 EPaNIC-RCT 的二次分析首先通过多变量线性回归分析，在匹配的早期-需要重症监护 ≥ 3 天的 PN 和晚期 PN 患者。其次，通过多变量逻辑回归和 Cox 比例风险分析，我们调查了晚期 PN 诱导的 CRP 是否会增加介导的感染预防和恢复，或者是否反映了抵消晚期 PN 的这些好处的不利影响。结果 CRP 在第 3 天达到峰值，晚期 PN [216(152-274)mg/l] (n = 946) 高于早期 PN [181(122-239)mg/l] (n = 946) ( p < 0.0001）。除了较高的血糖和血清胰岛素浓度 (p ≤ 0.01) 外，CRP 升高较高的独立决定因素是晚期 PN 的碳水化合物和蛋白质摄入量较低 (p ≤ 0.04)。晚期 PN 不影响细胞因子。较高的 CRP 升高与更多的感染和较低的早期 ICU 出院的可能性独立相关（p ≤ 0.002），并且在针对 CRP 升高进行调整后，晚期 PN 与早期 PN 对这些结果的影响大小增加而不是减少，未确认中介作用。结论 晚期 PN 时 CRP 升高较高（由早期常量营养素缺乏解释）与细胞因子反应无关，因此并未反映更多的全身性炎症。CRP 的升高并没有调解对感染或恢复的临床益处，而是降低了这种晚期 PN 益处的不利影响。