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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
.