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PCICS

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Early versus late parenteral nutrition in critically ill children

Fivez T. Van Den Berghe G et al. NEJM 2016;374:1111-1122

PubMed link: Early versus Late Parenteral Nutrition in Critically Ill Children.

Introduction:

  • Macro nutrient deficiency often develops in critically ill children after a few days
  • Current guidelines recommend the initiation of nutritional support soon after ICU admission. Once enteral nutrition fails, parental nutrition (PN) is advised. However there is inadequate evidence to support these recommendations, and recent large randomized controlled trials in critically ill adults have questioned the benefit of early PN.

Purpose of study: To determine whether a strategy of withholding parenteral nutrition up to date eight is clinically superior to the current practice of early printer up nutrition.
Methods:

Study design: Multicenter (n=3), prospective, randomized, controlled, parallel group superiority trial.

Patients:

  • Term newborns to children 17 years of age
  • Admitted to a pediatric ICU with anticipated ≥ 24 hours
  • Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) score ≥2

Intervention:

  • Early PN group: PN initiated within 24 hours after admission. PN supplemented any entral nutrition, with a goal of meeting local macronutrient and caloric targets.
  • Late PN group: PN withheld up to day 8 in the pediatric ICU.
    • D5 NS administered to match amount of IV fluid administered in early PN group.
  • In both groups:
    • Enteral nutrition was initiated early and increased in accordance with local guidelines.
    • Both study groups received intravenous micro nutrient starting on day 2.
    • On day 8, supplemental PN was provided for patients in both groups who are not yet receiving 80% of the caloric target enterally.
    • Glucose management and use of insulin infusions varied among centers based on local practice.

Endpoints:

  • Primary endpoints:
    • New infection during the ICU stay
    • Duration of ICU dependency
  • Secondary safety endpoints:
    • Death during the first seven days in the pediatric ICU, during total stay in the pediatric ICU, during late stay in the index hospital, and at 90 days after admission to the pediatric ICU and randomization
    • Number of patients with hypoglycemia
    • Number of readmissions to the pediatric ICU within 48 hours after discharge.
  • Secondary efficacy outcomes:
    • Time to final weaning from mechanical ventilatory support
    • Duration of pharmacologic or mechanical hemodynamic support
    • Proportion of patients receiving renal replacement therapy
    • Markers of liver dysfunction and inflammation
    • Time to live discharge from the hospital

Statistical analysis:

  • Intention to treat
  • Sample size based on 70% power to detect a five percentage point lower rate of new infection
  • Standard statistical methods were used, including multivariable modeling as appropriate.

Results:

  • 1440 patients were randomized and analyzed
  • Baseline characteristics were similar between the two groups
  • Primary outcomes:
    • New infection rate was 7.8% lower among children receiving late PN (adjusted OR, 0.48; 95% CI, 0.35 to 0.66).
    • Late PN was associated with a shorter stay in the pediatric ICU by a mean of 2.7 days (95% CI, 1.3 to 4.3), with a higher likelihood of earlier discharged alive from the ICU (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37).
      • A similar if not greater effect on these outcomes was seen in the 209 term neonates that were enrolled.
  • Secondary outcomes:
    • Mortality was similar in the two groups at all prespecified time points.
    • Duration of mechanical mandatory support was shorter and likelihood of being weaned alive earlier from mechanical ventilation was higher among patients receiving late PN.
    • No significant difference between groups in duration of hemodynamic support.
    • Late PN was associated with a lower need for renal replacement therapy.
    • Peak plasma total bilirubin levels were higher in the late PN group.
    • Peak plasma CRP levels were higher with late PN.
    • Mean duration of stay in the index hospital was 4.1 days shorter (95% CI, 1.4 to 6.6) and the likelihood of an earlier discharge alive from the hospital was higher (adjusted hazard ratio, 1.19; 95% CI, 1.07 to 1.33) in the late PN group.

Limitations: Staff providing intensive care were aware of treatment assignments

Conclusion: In critically ill children, withholding PN for one week while administering micronutrients intravenously was clinically superior to providing earlier PN to supplement insufficient enteral nutrition.