Abstract
Background & aims: Hypophosphatemia during critical illness has been associated with adverse outcome. The reintroduction of enteral or parenteral nutrition, leading to refeeding hypophosphatemia (RFH), has been presented as potential risk factor. We investigated the occurrence of early RFH, its association with clinical outcome, and the impact of early parenteral nutrition (PN) on the development of early RFH in pediatric critical illness. Methods: This is a secondary analysis of the PEPaNIC randomized controlled trial (N = 1440), which showed that withholding supplemental parenteral nutrition (PN) for 1 week (late-PN) in the pediatric intensive care unit (PICU) accelerated recovery and reduced new infections compared to early-PN (<24 h). Patients with renal replacement therapy or unavailable phosphate concentrations were excluded from this analysis. Early RFH was defined as serum/plasma phosphate <0.65 mmol/L and a drop of >0.16 mmol/L within 3 days of admission to the PICU. The association between baseline characteristics and early RFH, and the association of early RFH with clinical outcome were investigated using logistic and linear regression models, both uncorrected and corrected for possible confounders. To examine the impact of nutritional intake on phosphate concentrations, structural nested mean models with propensity score and censoring models were used. Results: A total of 1247 patients were eligible (618 early-PN, 629 late-PN). Early RFH occurred in 40 patients (3%) in total, significantly more in the early-PN group (n = 31, within-group occurrence 5%) than in the late-PN-group (n = 9, within-group occurrence 1%, p < 0.001). Patients who were older (OR 1.14 (95% CI 1.08; 1.21) per year added, p < 0.001) and who had a higher Pediatric Risk of Mortality (PIM3) score had a higher risk of developing early RFH (OR 1.36 (95% CI 1.15; 1.59) per unit added, p < 0.001), whereas patients in the late-PN group had a lower risk of early RFH (OR 0.24 (95% CI 0.10; 0.49), p < 0.001). Early RFH was significantly associated with a 56% longer PICU stay (p = 0.003) and 42% longer hospital stay (p = 0.007), but not with new infections (OR 2.01 (95% CI 0.90; 4.30), p = 0.08) or length of mechanical ventilatory support (OR 1.05 (95% CI −3.92; 6.03), p = 0.68), when adjusted for possible confounders. Increase of parenteral nutrition intake (in % kcal of predicted resting energy expenditure) decreased phosphate concentrations (c = −0.002 (95% CI -0.002; −0.001). Conclusions: Early RFH occurred in 3% of critically ill children. Patients randomized to late-PN had a lower chance of developing early RFH, which may be explained by the more gradual build-up of nutrition. As early RFH might impact recovery, it is important to closely monitor phosphate concentrations in patients, especially of those at risk for early RFH.
Original language | English |
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Pages (from-to) | 2500-2508 |
Number of pages | 9 |
Journal | Clinical Nutrition |
Volume | 41 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2022 |
Bibliographical note
Funding Information:This study was supported by ERC Advanced Grants AdvG-2012-321670 from the Ideas Program of the European Union 7th frame-work program and AdvG-2017-785809 to GVdB; by the Methusalem programme of the Flemish Government (through the University of Leuven to GVdB and IV, METH14/06); by the Agency for Innovation through Science and Technology, Flanders, Belgium (through the University of Leuven to GVdB, IWT/110685/TBM); by the University Hospitals Leuven (postdoctoral research fellowship by the Clinical Research and Education Council to JG); by the Sophia Children's Hospital Foundation (SSWO) to SCATV; by the Stichting Agis Zorginnovatie to SCATV; by the Erasmus Trustfonds to SCATV; and by a European Society for Clinical Nutrition and Metabolism (ESPEN) research grant to SCATV. The funders of the study had no role in the design of the study, the collection, analysis, and interpretation of data, or in the writing of the manuscript.
Publisher Copyright: © 2022 The Authors