Proefschrift Kerklaan

Chapter 5

found that the administration of growth hormone, with the intention to improve anabolism and outcome, improved nitrogen balances but increased mortality 26 . Also another large trial showed that early PN in adult ICU patients reduced markers of inflammation while it increased infections, weakness and organ failure and slowed down recovery 27 . Surrogate outcome measures are also the main focus of limited pediatric studies on glutamine-supplemented parenteral nutrition, that failed to show any advantage in critically ill children, just as enteral supplementation of glutamine 28 . Glutamine supplementation is no longer supported in adult critical care, based on the results of recent large high-quality RCTs that showed either no effect on morbidity or revealed and increased late mortality with glutamine supplementation 29-31 . In contrast to the PICU, there appears to be a greater consensus in the neonatal ICU, in favor of early parenteral supplementation. However, again the evidence generated by large RCTs with hard clinical endpoints is quite limited. In a Cochrane review, Trivedi et al 32 included 7 RCTs comparing the effect of intravenous early amino acid administration (within 24 hours after admission) with late initiation (>24 hours) in 394 low-birth-weight neonates on short-term in-hospital outcomes including mortality, early and late growth or neurodevelopment. There were no differences in length and occipitofrontal circumference, however nitrogen balance improved with early administration of amino acids. The impact on other outcomes was not reported. Only with early initiation of parenteral lipids, an improved neonatal growth has been suggested by two RCTs of very-low-birth-weight infants 33,34 . In contrast with the pediatric critically ill patient population, recent large and high quality trials have provided more evidence to support nutritional recommendations for adult critically ill patients 27,35-37 . The EPaNIC (the impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients trial) compared early parenteral supplementation of insufficient enteral feedingwith tolerating the caloric deficit that accumulateswhenonly EN is given in4640 adult ICU patients 27 . This study found that not using PN during the first week in ICU resulted in fewer new infections, less ICU acquired weakness with earlier weaning from mechanical ventilation 38 , less liver dysfunction 39 and reduced need for renal replacement therapy, together resulting in an earlier live discharge from the ICU and from the hospital 27 . The SPN (the impact of supplemental parenteral nutrition on infection rate, duration of mechanical ventilation and rehabilitation in ICU patients) trial compared the initiation of PN on day 4, when adult patients were not yet receiving 60% of their caloric needs, with tolerating a nutritional deficit with EN until day 8 37 . The SPN trial showed no differences in the clinically relevant outcomes. The early Parenteral Nutrition trial investigated whether PN should be started very early in critically ill patients when there was a short-term relative contra-indication to EN and apart from a shorter duration of mechanical ventilation (which was a tertiary outcome measure) there were no other clinical benefits 36 . The evidence generated from these trials has resulted in a change in clinical practice of adult intensive care, with a tendency to delay initiation of PN and to accept the macronutrient deficits for up to one week in ICU 40 .

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