Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Department of Anesthesia and Intensive Care, Jessa Hospital, Salvatorstraat 20, 3500, Hasselt, Belgium.
Intensive Care Med. 2022 Jan;48(1):25-35. doi: 10.1007/s00134-021-06565-1. Epub 2021 Nov 24.
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.
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.
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.
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.
在危重病早期停止肠外营养（PN），即晚期 PN，已被证明可以预防感染，尽管 C 反应蛋白（CRP）峰值较高。我们研究了这种加剧的 CRP 升高是由细胞因子介导的全身炎症效应引起的，还是由于不同的喂养方案引起的，以及它是否与晚期 PN 改善预后有关。
这项 EPaNIC-RCT 的二次分析首先通过多变量线性回归分析，研究了晚期 PN 引起的 CRP 升高的决定因素，以及其与需要重症监护≥3 天的匹配的早期 PN 和晚期 PN 患者的细胞因子反应（IL-6、IL-10、TNF-α）之间的关系。其次，通过多变量逻辑回归和 Cox 比例风险分析，我们研究了晚期 PN 引起的 CRP 升高是否介导了感染预防和恢复增强，或者反映了对抗晚期 PN 益处的不利影响。
CRP 在第 3 天达到峰值，晚期 PN 组[216（152-274）mg/l]（n=946）高于早期 PN 组[181（122-239）mg/l]（n=946）（p<0.0001）。晚期 PN 引起的 CRP 升高的独立决定因素是较低的碳水化合物和蛋白质摄入量（p≤0.04），此外还有较高的血糖和血清胰岛素浓度（p≤0.01）。晚期 PN 并未影响细胞因子。较高的 CRP 升高与更多感染和早期 ICU 出院的可能性较低独立相关（p≤0.002），并且在调整 CRP 升高后，晚期 PN 与早期 PN 对这些结果的影响大小增加而不是降低，这并不证实中介作用。
晚期 PN 引起的 CRP 升高更高，这可以用早期的宏量营养素缺乏来解释，与细胞因子反应无关，因此不反映更严重的全身炎症。晚期 PN 引起的 CRP 升高不是感染或恢复的临床获益的中介，而是一种降低这种晚期 PN 益处的不利影响。
