Lauwers C, Langouche L, Wouters P J, Wilmer A, Van den Berghe G, Casaer M P, Gunst J
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000, Leuven, Belgium.
Department of General Internal Medicine, University Hospitals Leuven, 3000, Leuven, Belgium.
Crit Care. 2025 Jan 28;29(1):48. doi: 10.1186/s13054-025-05273-2.
As compared to withholding parenteral nutrition (PN) until one week after intensive care unit (ICU) admission, Early PN prolonged ICU dependency in the EPaNIC randomized controlled trial (RCT). The Refeeding RCT showed improved outcome by temporary macronutrient restriction in ICU patients developing refeeding hypophosphatemia, defined as a phosphate decrease of > 0.16 mmol/L to levels < 0.65 mmol/L. We hypothesized that early phosphate changes may identify critically ill patients who are harmed by Early PN, and that dynamic phosphate changes are more discriminative than an absolute threshold for hypophosphatemia.
In this secondary analysis of the EPaNIC RCT, we studied whether absolute hypophosphatemia (AHP; < 0.65 mmol/L on the second ICU-day), relative hypophosphatemia (RHP; > 0.16 mmol/L decrease over the first 2 ICU-days), or a combination of both (CHP) interacted with the randomized nutritional strategy for its impact on outcome, adjusted for risk factors. In case of significant interaction, we studied whether the respective change could be predicted by baseline characteristics.
Of 3520 patients with available phosphate measurements, AHP developed in 9.1%, RHP in 23.7%, and CHP in 5.3% of patients. RHP, but not AHP or CHP, interacted with the randomized intervention for its impact on outcome (p = 0.01). In RHP patients, Early PN independently associated with a lower likelihood of an earlier discharge alive from ICU (adjusted HR 0.75 [0.65-0.87]). In patients without RHP, Early PN did not significantly associate with this outcome (adjusted HR 0.93 [0.86-1.00]). Development of RHP was only poorly predicted by admission characteristics (adjusted pseudo R-squared = 1.7%).
Development of RHP may identify patients who are particularly harmed by early PN. Future studies should prospectively validate the potential of including RHP in a ready-to-feed indicator.
在EPaNIC随机对照试验（RCT）中，与在重症监护病房（ICU）入院一周后再给予肠外营养（PN）相比，早期PN延长了ICU依赖时间。再喂养RCT显示，对于发生再喂养低磷血症（定义为磷酸盐下降>0.16 mmol/L至<0.65 mmol/L）的ICU患者，通过临时限制大量营养素可改善预后。我们假设早期磷酸盐变化可能识别出因早期PN而受到伤害的危重症患者，并且动态磷酸盐变化比低磷血症的绝对阈值更具鉴别力。
在对EPaNIC RCT的这项二次分析中，我们研究了绝对低磷血症（AHP；在ICU第二天<0.65 mmol/L）、相对低磷血症（RHP；在前两个ICU日下降>0.16 mmol/L）或两者的组合（CHP）是否与随机营养策略相互作用，以影响预后，并对风险因素进行了调整。如果存在显著相互作用，我们研究了各自的变化是否可由基线特征预测。
在3520例有可用磷酸盐测量值的患者中，9.1%的患者发生了AHP，23.7%的患者发生了RHP，5.3%的患者发生了CHP。RHP与随机干预对预后的影响存在相互作用（p = 0.01），而AHP或CHP则不存在。在RHP患者中，早期PN与从ICU更早存活出院的可能性较低独立相关（校正风险比0.75 [0.65 - 0.87]）。在没有RHP的患者中，早期PN与该预后无显著关联（校正风险比0.93 [0.86 - 1.00]）。入院特征对RHP发生的预测能力较差（校正伪R平方 = 1.7%）。
RHP的发生可能识别出特别容易因早期PN而受到伤害的患者。未来的研究应前瞻性地验证将RHP纳入即食指标的潜力。
