Plasma and red blood cell concentrations of zinc, copper, selenium and magnesium in the first week of paediatric critical illness.

BACKGROUND & AIMS: Critically ill children are at risk of micronutrient deficiencies, which might lead to poor clinical outcomes. However, the interpretation of micronutrient concentrations in plasma is complicated due to age-dependent and critical illness-dependent changes. Certain red blood cell (RBC) concentrations might reflect the overall body status more reliably than plasma levels in the presence of systemic inflammatory response. This study longitudinally examined micronutrient concentrations in both plasma and RBC in critically ill children. METHODS: This secondary analysis of the PEPaNIC RCT investigated the impact of early versus late initiation of parenteral macronutrient supplementation in critically ill children. All children received micronutrients when EN was insufficient (<80 % energy requirements). Blood samples were obtained on days 1, 3, 5 and 7 of Paediatric Intensive Care Unit (PICU) admission. Inductively coupled plasma mass spectrometry was used to measure zinc, selenium, and copper in plasma and selenium, copper, and magnesium in RBCs. Plasma magnesium was measured with colorimetric detection. Micronutrient concentrations were compared with age-specific reference values in healthy children and expressed using Z-scores. Changes in micronutrient concentrations over time were examined using the Friedman and post hoc Wilcoxon signed-rank tests. RESULTS: For 67 critically ill children, median (Q1; Q3) age 9.5 (5.5; 13.2) years, PIM3 score -2.3 (-3.1; -0.8), samples were available at various time points during their PICU stay. For 22 patients, longitudinal samples were available. On day 1, the median plasma Z-score for zinc was -5.2 (-5.2; -2.9), copper -1.6 (-2.9; -0.2), selenium -2.6 (-3.8; -1.0), magnesium -0.2 (-1.6; 1.3), and median RBC Z-score for copper was 0.5 (-0.1; 1.3), selenium -0.3 (-1.1; 0.7), magnesium 0.2 (-0.4; 1.3). In the longitudinal analysis, plasma zinc was significantly higher on day 5 (Z-score -3.2 (-4.6; -1.4)) than on day 1 (Z-score -5.2 (-5.2; -3.0), p = 0.032), and plasma magnesium was significantly higher on day 3 (Z-score 1.1 (-0.7; 4.0)) than on day 1 (Z-score -0.3 (-1.6; 0.5), p = 0.018). Plasma copper and selenium remained stable, and the RBC concentrations of all micronutrients remained stable during the first five days. CONCLUSIONS: Most patients had low plasma zinc, copper and selenium concentrations in the first week of their PICU stay, whereas they had normal to high RBC concentrations. More research is needed to examine the relationships between micronutrients and clinical outcome.

Early hypophosphatemia in critically ill children and the effect of parenteral nutrition: A secondary analysis of the PEPaNIC RCT.

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.

Glucose homeostasis, nutrition and infections during critical illness.

Critical illness is a complex life-threatening disease characterized by profound endocrine and metabolic alterations and by a dysregulated immune response, together contributing to the susceptibility for nosocomial infections and sepsis. Hitherto, two metabolic strategies have been shown to reduce nosocomial infections in the critically ill, namely tight blood glucose control and early macronutrient restriction. Hyperglycaemia, as part of the endocrine-metabolic responses to stress, is present in virtually all critically ill patients and is associated with poor outcome. Maintaining normoglycaemia with intensive insulin therapy has been shown to reduce morbidity and mortality, by prevention of vital organ dysfunction and prevention of new severe infections. The favourable effects of this intervention were attributed to the avoidance of glucose toxicity and mitochondrial damage in cells of vital organs and in immune cells. Hyperglycaemia was shown to impair macrophage phagocytosis and oxidative burst capacity, which could be restored by targeting normoglycaemia. An anti-inflammatory effect of insulin may have contributed to prevention of collateral damage to host tissues. Not using parenteral nutrition during the first week in intensive care units, and so accepting a large macronutrient deficit, also resulted in fewer secondary infections, less weakness and accelerated recovery. This was at least partially explained by a suppressive effect of early parenteral nutrition on autophagic processes, which may have jeopardized crucial antimicrobial defences and cell damage removal. The beneficial impact of these two metabolic strategies has opened a new field of research that will allow us to improve the understanding of the determinants of nosocomial infections, sepsis and organ failure in the critically ill.